記述言語：英語   掲載種別：研究論文（学術雑誌）  

The renin-angiotensin system in the brain plays a pivotal role in modulating sympathetic nerve activity and contributes to the pathogenesis of hypertension. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R while suppressing pathological overactivation of AT1R signaling. However, the pathophysiological function of ATRAP in the brain remains unknown. Therefore, this study aims to investigate whether ATRAP in the paraventricular nucleus (PVN) is involved in neurogenic hypertension pathogenesis in Ang II-infused rats. The ATRAP/AT1R ratio, which serves as an indicator of tissue AT1R hyperactivity, tended to decrease within the PVN in the Ang II group than in the vehicle group. This suggests an Ang II-induced hyperactivation of the AT1R signaling pathway in the PVN. Lentiviral vectors were generated to stimulate ATRAP expression. At 6 weeks of age, rats were microinjected with LV-Venus (Venus-expressing lentivirus) or LV-ATRAP (Venus-ATRAP-expressing lentivirus). The rats were then randomly divided into four groups: (1) Vehicle/LV-Venus, (2) Vehicle/LV-ATRAP, (3) Ang II/LV-Venus, and (4) Ang II/LV-ATRAP. Two weeks after microinjection, vehicle or Ang II was administered systemically for 2 weeks. In the Ang II/LV-ATRAP group, systolic blood pressure at 1 and 2 weeks following administration was significantly lower than that in the Ang II/LV-Venus group. Furthermore, urinary adrenaline levels tended to decrease in the Ang II/LV-ATRAP group than in the Ang II/LV-Venus group. These findings suggest that enhanced ATRAP expression in the PVN suppresses Ang II-induced hypertension, potentially by suppressing hyperactivation of the tissue AT1R signaling pathway and, subsequently, sympathetic nerve activity.

DOI： 10.1038/s41440-023-01480-y

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Corneal astigmatism is reportedly associated with polymorphisms of the platelet-derived growth factor receptor alpha (PDGFRA) gene region in Asian populations of Chinese, Malay, and Indian ancestry and populations of European ancestry. In this study, we investigated whether these PDGFRA polymorphisms are associated with corneal astigmatism in a Japanese population. We recruited 1,535 cases with corneal astigmatism (mean corneal cylinder power across both eyes: ≤  - 0.75 diopters [D]) and 842 controls (> - 0.75 D) to genotype 13 single-nucleotide polymorphisms (SNPs) in the PDGFRA gene region. We also performed imputation analysis in the region, with 179 imputed SNPs included in the statistical analyses. The PDGFRA SNPs were not significantly associated with the cases with corneal astigmatism ≤  - 0.75 D. However, the odds ratios (ORs) of the minor alleles of SNPs in the upstream region of PDGFRA, including rs7673984, rs4864857, and rs11133315, tended to increase according to the degree of corneal astigmatism, and these SNPs were significantly associated with the cases with corneal astigmatism ≤  - 1.25 D or ≤  - 1.50 D (Pc < 0.05, OR = 1.34-1.39). These results suggest that PDGFRA SNPs play a potential role in the development of greater corneal astigmatism.

DOI： 10.1038/s41598-023-43333-1

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Spinal cord injury in teleosts leads to a fibrous scar, but axons sometimes spontaneously regenerate beyond the scar. In goldfish, regenerating axons enter the scar through tubular structures and enlargement of the tubular diameter is proportional to the increase in the number of regenerating axons. During the regeneration process, mast cells containing 5-hydroxytryptamine (5HT) are recruited to the injury site, and 5HT neurons are newly generated. Here, we investigated the distribution of 5HT receptors during this process to determine their role in remodeling the fibrous scar and tubular structures. At 2 weeks after spinal cord transection (SCT) in goldfish, expression of the 5HT2A and 5HT2C receptor subtypes was observed in the ependymo-radial glial cells lining the central canal of the spinal cord. 5HT2A was expressed at the luminal surface, suggesting that it is receptive to 5HT in the cerebrospinal fluid. 5HT2C, on the other hand, was expressed around the nuclei and in the radial processes protruding from the basal surface, suggesting that it is receptive to 5HT released from nearby nerve endings. 5HT2C was also expressed in the fibrous scar where mast cells containing 5HT were abundant. 5HT1B expression was coincident with the basement membrane bordering the fibrous scar and the surrounding nervous tissue, and with the basement membrane of the tubular structure through which axons pass during regeneration. Our findings suggest that multiple 5HT receptors are involved in remodeling the injured site during the regenerative process following SCT. Ependymo-radial glial cells expressing 5HT2A and 5HT2C are involved in neurogenesis and gliogenesis, which might contribute to remodeling the fibrous scar in coordination with 5HT-containing mast cells. Coincident expression of 5HT1B with the basement membrane might be involved in remodeling the tubular structures, thereby promoting axonal regeneration.

DOI： 10.1016/j.jchemneu.2023.102281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.

DOI： 10.3390/ijms24097778

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1227/neuopn.0000000000000019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type 2 diabetes (T2DM); however, the pathological significance of this increase in UCP2 expression is unclear. In this study, we highlight the molecular link between the increase in UCP2 expression in β-cells and β-cell failure by using genetically engineered mice and human islets. β-cell-specific UCP2-overexpressing transgenic mice (βUCP2Tg) exhibited glucose intolerance and a reduction in insulin secretion. Decreased mitochondrial function and increased aldolase B (AldB) expression through oxidative-stress-mediated pathway were observed in βUCP2Tg islets. AldB, a glycolytic enzyme, was associated with reduced insulin secretion via mitochondrial dysfunction and impaired calcium release from the endoplasmic reticulum (ER). Taken together, our findings provide a new mechanism of β-cell dysfunction by UCP2 and AldB. Targeting the UCP2/AldB axis is a promising approach for the recovery of β-cell function.

DOI： 10.1016/j.isci.2022.104603

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chondroitinase ABC (ChABC) is an enzyme that degrades glycosaminoglycan side-chains of chondroitin sulfate (CS-GAG) from the chondroitin sulfate proteoglycan (CSPG) core protein. Previous studies demonstrated that the administration of ChABC after spinal cord injury promotes nerve regeneration by removing CS-GAGs from the lesion site and promotes the plasticity of spinal neurons by removing CS-GAGs from the perineuronal nets (PNNs). These effects of ChABC might enhance the regeneration and sprouting of descending axons, leading to the recovery of motor function. Anatomical evidence, indicating that the regenerated axons innervate spinal motoneurons caudal to the lesion site, however, has been lacking. In the present study, we investigated whether descending axons pass through the lesion site and innervate the lumbar motoneurons after ChABC administration in rats with complete spinal cord transection (CST) at the thoracic level. At 3 weeks after CST, 5-hydroxytryptamine (5-HT) fibers were observed to enter the lesion in ChABC-treated rats, but not saline-treated rats. In addition, 92% of motoneurons in the ventral horn of the fifth lumbar segment (L5) in saline-treated rats, and 38% of those in ChABC-treated rats were surrounded by chondroitin sulfate-A (CS-A) positive structures. At 8 weeks after CST, many 5-HT fibers were observed in the ventral horn of the L5, where they terminated in the motoneurons in ChABC-treated rats, but not in saline-treated rats. In total, 54% of motoneurons in the L5 ventral horn in saline-treated rats and 39% of those in ChABC-treated rats were surrounded by CS-A-positive structures. ChABC-treated rats had a Basso, Beattie, and Bresnahan (BBB) motor score of 3.8 at 2 weeks, 7.1 at 3 weeks, and 10.3 at 8 weeks after CST. These observations suggest that ChABC administration to the lesion site immediately after CST may promote the regeneration of descending 5-HT axons through the lesion site and their termination on motoneurons at the level of caudal to the lesion site. ChABC administration might facilitate reinnervation by degrading CS-GAGs around motoneurons. Motor function of the lower limbs was significantly improved in ChABC-treated rats even before the 5-HT axons terminated on the motoneurons, suggesting that other mechanisms may also contribute to the motor function recovery.

DOI： 10.3389/fnint.2022.881632

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the acute phase of spinal cord injury, the initial injury triggers secondary damage due to neuroinflammation, leading to the formation of cavities and glial scars that impair nerve regeneration. Following injuries to the central nervous system, early mobilization promotes the recovery of physical function. Therefore, in the present study, we investigated the effects of early mobilization on motor function recovery and neuroinflammation in rats. Early mobilization of rats with complete spinal cord transection resulted in good recovery of hindlimb motor function after 3 weeks. At 1 week after spinal cord injury, the early-mobilized rats expressed fewer inflammatory M1 microglia/macrophages and more anti-inflammatory M2 microglia. In addition, significantly more matrix metalloproteinase 2 (MMP2)-positive cells were observed at the lesion site 1 week after injury in the early-mobilized rats. Multiple labeling studies suggested that many MMP2-positive cells were M2 microglia. MMP9-positive cells that highly co-expressed GFAP were also observed more frequently in the early-mobilized rats. The density of growth-associated protein-positive structures in the lesion center was significantly higher in the early-mobilized rats at 3 weeks after spinal cord injury. The present results suggest that early mobilization after spinal cord injury reduced the production of M1 microglia/macrophages while increasing the production of M2 microglia at the lesion site. Early mobilization might also activate the expression of MMP2 in M2 microglia and MMP9 in astrocytes. These cellular dynamics might suppress neuroinflammation at the lesion site, thereby inhibiting the progression of tissue destruction and promoting nerve regeneration to recover motor function.

DOI： 10.1016/j.ibneur.2022.04.002

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The thalamic reticular nucleus (TRN) projects inhibitory signals to the thalamus, thereby controlling thalamocortical connections. Few studies have examined the development of TRN projections to the anterior thalamic nuclei with regard to axon course and the axon terminal distributions. In the present study, we used parvalbumin (PV) immunostaining to investigate inhibitory projections from the TRN to the thalamus in postnatal (P) 2- to 5-week-old rats (P14-35). The distribution of PV-positive (+) nerve fibers and nerve terminals markedly differed among the anterior thalamic nuclei at P14. Small, beaded nerve terminals were more distributed throughout the anterodorsal nucleus (AD) than in the anteroventral nucleus (AV) and anteromedial nucleus (AM). PV+ fibers traveling from the TRN to the AD were observed in the AV and AM. Nodular nerve terminals, spindle or en passant terminals, were identified on the axons passing through the AV and AM. At P21, axon bundles traveling without nodular terminals were observed, and nerve terminals were distributed throughout the AV and AM similar to the AD. At P28 and P35, the nerve terminals were evenly distributed throughout each nucleus. In addition, DiI tracer injections into the retrosplenial cortex revealed retrogradely-labeled projection neurons in the 3 nuclei at P14. At P14, the AD received abundant projections from the TRN and then projected to the retrosplenial cortex. The AV and AM seem to receive projections with distinct nodular nerve terminals from the TRN and project to the retrosplenial cortex. The projections from TRN to the AV and AM with nodular nerve terminals at P14 are probably developmental-period specific. In comparison, the TRN projections to the AD at P14 might be related to the development of spatial navigation as part of the head orientation system.

DOI： 10.4081/ejh.2022.3370

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hind limb locomotor activity spontaneously recovers after complete spinal transection (CST) in neonatal rats, but the mechanisms underlying the recovery are poorly understood. The perineuronal net (PNN) surrounding the neuronal cell bodies comprises an extracellular matrix that regulates neuronal plasticity during development. Here, we examined the expression of chondroitin sulfate (CS), a major component of the PNN, on motoneurons after CST in neonatal rats, and compared it with that in juvenile rats, in which hindlimb locomotor activity does not recover spontaneously. The spinal cord was transected at the mid-thoracic level in neonatal (postnatal day 5 [P5] and P10) and juvenile (P15 and P20) rats. Two weeks after CST, the percentage of motoneurons surrounded by chondroitin sulfate C (CS-C) - positive structures was significantly lower in rats with CST at P10 than in intact rats, and tended to be higher in rats with CST at P15 than in intact rats. The percentage of motoneurons with CS-A - positive structures was significantly lower in rats with CST at P15 than in intact rats. These findings suggest that CS-A and CS-C are differentially expressed in the PNNs in rats with CST. The decrease in CS-C - positive PNNs might facilitate the formation of new synaptic contacts to motoneurons, resulting in the recovery of the hindlimb locomotor activity in rats with CST during the neonatal period.

DOI： 10.1016/j.neulet.2021.136324

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Spinal cord injury in fish produces fibrous scar, but spontaneous axonal regeneration beyond the scar sometimes occurs. A previous study revealed that regenerating axons enter the scar through tubular structures with laminin, and that an increased number of axons within the tube is coincident with enlargement of the tube diameter and reduction of the fibrous scar area. The present study investigated the expression of matrix metalloproteinases (MMPs) that might play a role in the degradation of the extracellular matrix in fibrous scar tissue and in the remodeling of tubular structures. Spinal hemisection produced fibrous scar tissue in the lesion center, surrounded by nervous tissue. Two weeks after spinal lesioning, MMP-9 was expressed in some regenerating axons in the fibrous scar tissue. MMP-14 was expressed in the regenerating axons, as well as in glial processes in the fibrous scar tissue. MMP-2 was suggested to be expressed in mast cells in the fibrous scar. The mast cells were in contact with fibroblasts, and in close proximity to the basement membrane of tubular structures surrounding the regenerating axons. The present findings suggest that several MMPs are involved in axon regenerating processes following spinal cord injury in goldfish. MMP-9 and MMP-14 expressed in the regenerating axons might degrade extracellular matrix and support axonal growth deep into the fibrous scar tissue. MMP-14 expressed in glial cells and MMP-2 expressed in mast cells might also provide a beneficial environment for axonal regeneration, leading to successful motor recovery.

DOI： 10.1016/j.jchemneu.2021.102041

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The kidney is one of the most susceptible organs to age-related impairments. Generally, renal aging is accompanied by renal fibrosis, which is the final common pathway of chronic kidney diseases. Aristolochic acid (AA), a nephrotoxic agent, causes AA nephropathy (AAN), which is characterized by progressive renal fibrosis and functional decline. Although renal fibrosis is associated with renal aging, whether AA induces renal aging remains unclear. The aim of the present study is to investigate the potential use of AAN as a model of renal aging. Here, we examined senescence-related factors in AAN models by chronically administering AA to C57BL/6 mice. Compared with controls, the AA group demonstrated aging kidney phenotypes, such as renal atrophy, renal functional decline, and tubulointerstitial fibrosis. Additionally, AA promoted cellular senescence specifically in the kidneys, and increased renal p16 mRNA expression and senescence-associated β-galactosidase activity. Furthermore, AA-treated mice exhibited proximal tubular mitochondrial abnormalities, as well as reactive oxygen species accumulation. Klotho, an antiaging gene, was also significantly decreased in the kidneys of AA-treated mice. Collectively, the results of the present study indicate that AA alters senescence-related factors, and that renal fibrosis is closely related to renal aging.

DOI： 10.3390/ijms222212432

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nicotine exerts its reinforcing actions by activating nicotinic acetylcholine receptors (nAChRs), but the detailed mechanisms remain unclear. Nicotine releases 3, 4-dihydroxyphenylalanine (DOPA), a neurotransmitter candidate in the central nervous system. Here, we investigated the distribution of GPR143, a receptor of DOPA, and nAChR subunits in the nigrostriatal and mesolimbic regions. We found GPR143 mRNA-positive cells in the striatum and nucleus accumbens. Some of them were surrounded by tyrosine hydroxylase (TH)-immunoreactive fibers. There were some GPR143 mRNA-positive cells coexpressing TH, and nAChR subunit α4 or α7 in the substantia nigra and ventral tegmental area. These findings suggest that DOPA-GPR143 signaling may be involved in the nicotine action in the nigrostriatal and mesolimbic dopaminergic systems.

DOI： 10.1016/j.neures.2020.08.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy. METHODS: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements. RESULTS: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved. CONCLUSIONS: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

DOI： 10.1016/j.wneu.2021.04.041

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Perineuronal nets are extracellular matrix structures that surround neuronal cell bodies and their proximal dendrites in the central nervous system. Chondroitin sulfate proteoglycans, which contain chondroitin sulfates (CSs) are major components of perineuronal nets. CSs are considered to have inhibitory roles in neural plasticity, although the effects differ according to their sulfation pattern. In the present study, we investigated the expression of the CS subtypes CS-A and CS-C surrounding spinal motoneurons in different postnatal periods to explore the potential influence of altered CS sulfation patterns on spinal development. CS-A-positive structures were observed around motoneurons in the cervical, thoracic, and lumbar segments as early as postnatal day (P) 5. Most motoneurons were covered with CS-A-positive structures during the first 2 postnatal weeks. The percentage of motoneurons covered with CS-A-positive structures decreased after P20, becoming lower than 70% in the cervical, and lumber segments after P35. CS-C-positive structures were occasionally observed around motoneurons during the first 2 postnatal weeks. The percentage of motoneurons covered with CS-C-positive structures increased after P20, becoming significantly higher after P25 than before P20. The expression pattern of Wisteria Floribunda agglutinin-positive structures around motoneurons was similar to that of the CS-C-positive structures. The present findings revealed that CS-A and CS-C are differentially expressed in the extracellular matrix surrounding motoneurons. The altered sulfation pattern with increased CS-C expression is associated with the maturation of perineuronal nets and might lead to changes in the motoneuron plasticity.

DOI： 10.1016/j.brainres.2020.147252

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a unique enzyme introducing O-GlcNAc moiety on target proteins, and it critically regulates various cellular processes in diverse cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) remain elusive. Here, using Ogt conditional knockout mice, we show that OGT is essential for HSPCs. Ogt is highly expressed in HSPCs, and its disruption induces rapid loss of HSPCs with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient hematopoietic stem cells (HSCs) lose quiescence, cannot be maintained in vivo, and become vulnerable to regenerative and competitive stress. Interestingly, Ogt-deficient HSCs accumulate defective mitochondria due to impaired mitophagy with decreased key mitophagy regulator, Pink1, through dysregulation of H3K4me3. Furthermore, overexpression of PINK1 restores mitophagy and the number of Ogt-deficient HSCs. Collectively, our results reveal that OGT critically regulates maintenance and stress response of HSCs by ensuring mitochondrial quality through PINK1-dependent mitophagy.

DOI： 10.1016/j.celrep.2020.108579

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Exosomes contain many proteins associated with neurodegenerative diseases. To identify new candidate biomarkers and proteins associated with amyotrophic lateral sclerosis (ALS), we performed liquid chromatography-tandem mass spectrometry proteomic analysis of exosome-enriched fractions isolated from cerebrospinal fluid (CSF) of sporadic ALS patients using gel filtration chromatography. Proteomic data revealed that three proteins were increased and 11 proteins were decreased in ALS patients. The protein with the greatest increase in exosome-enriched fractions of CSF derived from ALS was novel INHAT repressor (NIR), which is closely associated with nucleolar function. By immunohistochemical analysis, we found that NIR was reduced in the nucleus of motor neurons in ALS patients. Our results demonstrate the potential utility of our methodology for proteomic analysis of CSF exosomes and suggest that nucleolar stress might play a role in sporadic ALS pathogenesis through the dysfunction of NIR.

DOI： 10.1016/j.neures.2019.10.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

DOI： 10.1007/s12565-020-00545-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Insoluble hyaluronic acid (IHA) may prevent adhesions by forming a physical barrier during the period when postoperative adhesions form. This study was performed to verify the changes that a solid IHA membrane undergoes as it is degraded in vivo, and to ascertain the swelling rate of IHA required for it to function as a physical barrier during the postoperative adhesion formation period. Nine female WI rats weighing 300-400 g were used. Discs 8 mm in diameter were cut out of dry IHA membranes made of IHA with a swelling rate (wet weight/dry weight) of either 2.47 (high-swelling IHA) or 1.94 (low-swelling IHA). They were placed in saline to swell and then washed with saline before subcutaneous implantation in four pockets in each rat. The high-swelling IHA started to degrade more rapidly than the low-swelling IHA. There was no evidence of degradation of the low-swelling IHA until day 7, but once it had started, the speed of degradation tended to be similar to that of the high-swelling IHA. The present results showed that, when IHA is implanted subcutaneously in rats, it is degraded over time in a phased process. The swelling rate required for the use of IHA as a postoperative adhesion barrier was also suggested.

DOI： 10.1016/j.bbrc.2018.09.151

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Complete spinal transection in adult rats results in poor recovery of hind limb function and severe urinary bladder dysfunction. Neonatal rats with spinal cord transection, however, exhibit spontaneous and significant recovery of micturition control. A previous study in which biotinylated-dextran amine (BDA) was used as an anterograde tracer demonstrated that primary afferent fibers from the fifth lumbar dorsal root ganglion (DRG) project more strongly and make more terminals in the ventral horn after neonatal spinal cord transection at the mid-thoracic level. In the present study, we injected BDA into the sixth lumbar (L6) DRG of neonatally spinalized rats to label primary afferent fibers that include visceral afferents. The labeled fibers projected to the intermediolateral nucleus (IML) in the intermediate zone on ipsilateral side of the L6 spinal segment, whereas no projections to the IML were observed in sham-operated or intact rats. The BDA-labeled fibers of neonatally spinalized rats formed varicose terminals on parasympathetic preganglionic neurons in the IML. These findings suggest that some primary afferent projections from the L6 DRG to the IML appear after neonatal spinal cord transection, and these de novo projections might contribute to the recovery of autonomic function such as micturition following spinal cord injury in the neonatal stage.

添付ファイル： 1-s2.0-S2451830117300183-main.pdf

DOI： 10.1016/j.ibror.2017.11.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Mary Ann Liebert Inc.  

For the treatment of acute cervical spinal cord injuries, a local epidural cooling system using a percutaneous technique was proposed. In this animal study, regional low temperature was obtained stably in the cervical epidural space (CED) without decreasing temperatures at the rectum and the thoracic epidural space. Three stainless steel tubes were inserted percutaneously using the lateral approach into 3 serial interspinous spaces of the neck of 12 beagles under radiographic guidance. Two temperature probes were inserted into the CEDs at the level of the middle cooling tube. A third temperature probe was inserted into the epidural space at the Th13 level. A fourth temperature probe was placed in the rectum as a control. Iced water was circulated in the cooling tubes for 60 minutes. Temperatures were monitored every 10 seconds for 90 minutes, with the minimum temperatures during the period being recorded. The mean minimum temperatures recorded in the dorsal CED (min-CED-dorsal), the lateral CED (min-CED-lateral), the Th13 epidural space (min-T13ED), and the rectum (min-rectum), were 16.0 ± 0.6°C, 22.6 ± 1.6°C, 35.4 ± 0.2°C, and 35.5 ± 0.2°C, respectively. There was a statistically significant difference between the mean min-CED-dorsal and min-rectum temperatures (p < 0.0001). The method introduced above was effective in reducing cervical epidural temperature selectively.

DOI： 10.1089/ther.2017.0013

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media S.A.  

Perineuronal nets (PNNs) surrounding neuronal cell bodies regulate neuronal plasticity during development, but their roles in regeneration are unclear. In the PNNs, chondroitin sulfate (CS) is assumed to be involved in inhibiting contact formation. Here, we examined CS expression in PNNs in the ventral horn of a goldfish hemisected spinal cord in which descending axons regenerate beyond the lesion to connect with distal spinal neurons. In intact fish, chondroitin sulfate A (CS-A)-positive PNNs accounted for 5.0% of HuC/D-immunoreactive neurons, and 48% of choline acetyltransferase (ChAT)-immunoreactive neurons. At 2, 4 and 8 weeks after spinal hemisection, CS-A-positive PNNs accounted for 8.4%-9.9% of HuC/D-immunoreactive neurons, and 50%-60% of ChAT-immunoreactive neurons, which was not significantly different from intact fish. Chondroitin sulfate C (CS-C)-positive PNNs accounted for 6.4% of HuC/D-immunoreactive neuron, and 67% of ChAT-immunoreactive neurons in intact fish. At 2, 4 and 8 weeks after spinal hemisection, CS-C-positive PNNs accounted for 7.9%, 5.5% and 4.3%, respectively, of HuC/D-immunoreactive neurons, and 65%, 52% and 42%, respectively, of ChAT-immunoreactive neurons, demonstrating a significant decrease at 4 and 8 weeks after spinal hemisection. Among ventral horn neurons that received descending axons labeled with tetramethylrhodamine dextran amine (RDA) applied at the level of the first spinal nerve, CS-A-positive PNNs accounted for 53% of HuC/D-immunoreactive neurons. At 2 and 4 weeks after spinal hemisection, CS-A-positive PNNs accounted for 57% and 56% of HuC/D-immunoreactive neurons, which was not significantly different from intact fish. CS-C-positive PNNs, accounted for 48% of HuC/D-immunoreactive neurons that received RDA-labeled axons. At 2 and 4 weeks after spinal hemisection, CS-C-positive PNNs significantly decreased to 22% of the HuC/D-immunoreactive neurons, and by 4 weeks after spinal hemisection they had returned to 47%. These findings suggest that CS expression is maintained in the PNNs after spinal cord lesion, and that the descending axons regenerate to preferentially terminate on neurons not covered with CS-C-positive PNNs. Therefore, CS-C in the PNNs possibly inhibits new contact with descending axons, and plasticity in the spinal neurons might be endowed by downregulation of CS-C in the PNNs in the regeneration process after spinal hemisection in goldfish.

添付ファイル： fncel-12-00063.pdf

DOI： 10.3389/fncel.2018.00063

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Chondroitin sulfate proteoglycans produced in glial scar tissue are a major inhibitory factor for axonal regeneration after central nervous system injury in mammals. The inhibition is largely due to chondroitin sulfates, whose effects differ according to the sulfation pattern. In contrast to mammals, fish nerves spontaneously regenerate beyond the scar tissue after spinal cord injury, although the mechanisms that allow for axons to pass through the scar are unclear. Here, we used immunohistochemistry to examine the expression of two chondroitin sulfates with different sulfation variants at the lesion site in goldfish spinal cord. The intact spinal cord was immunoreactive for both chondroitin sulfate-A (CS-A) and chondroitin sulfate-C (CS-C), and CS-A immunoreactivity overlapped extensively with glial processes positive for glial fibrillary acidic protein. At 1week after inducing the spinal lesion, CS-A immunoreactivity was observed in the cell bodies and extracellular matrix, as well as in glial processes surrounding the lesion center. At 2weeks after the spinal lesion, regenerating axons entering the lesion center overtook the CS-A abundant area. In contrast, at 1week after lesion induction, CS-C immunoreactivity was significantly decreased, and at 2weeks after lesion induction, CS-C immunoreactivity was observed along the regenerating axons entering the lesion center. The present findings suggest that after spinal cord injury in goldfish, chondroitin sulfate proteoglycans are deposited in the extracellular matrix at the lesion site but do not form an impenetrable barrier to the growth of regenerating axons.

DOI： 10.1016/j.brainres.2017.08.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Axonal regeneration in the adult mammalian central nervous system is limited in part by the non-permissive environment, including axonal growth inhibitors such as the Nogo-A protein. How the functions of these inhibitors can be blocked remains unclear. Here, we examined the role of LOTUS, an endogenous Nogo receptor antagonist, in promoting functional recovery and neural repair after spinal cord injury (SCI), as well as axonal regeneration after optic nerve crush. Wild-type untreated mice show incomplete but substantial intrinsic motor recovery after SCI. The genetic deletion of LOTUS delays and decreases the extent of motor recovery, suggesting that LOTUS is required for spontaneous neural repair. The neuronal overexpression of LOTUS in transgenic mice promotes motor recovery after SCI, and recombinant viral overexpression of LOTUS enhances retinal ganglion cell axonal regeneration after optic nerve crush. Thus, the level of LOTUS function titrates axonal regeneration.

DOI： 10.1038/s41598-017-12449-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

The caudal part of the corpus cerebelli of Nile tilapia can be divided into dorsal and ventral regions. The granule cell layer of the dorsal (dGL) and ventral (vGL) regions of the caudal corpus cerebelli is known to receive indirect inputs from the telencephalon relayed by the nucleus paracommissuralis. The descending pathways are topographically organized, and the dGL and vGL receive inputs from different dorsal telencephalic parts. The caudal corpus cerebelli, in turn, projects extracerebellar efferents. However, it remains unknown how the descending telencephalic inputs are processed within the cerebellum. Therefore, the present study investigated intrinsic connections of the caudal corpus cerebelli by injecting neural tracers into the molecular layer of dorsal and ventral regions. Injections of tracers into the ventral molecular layer resulted in labeled cells in the vGL and the ganglionic layer of the ventral corpus. The axonal trajectories from labeled cells in the ganglionic layer were analyzed in detail via single-axon reconstructions, which suggested that the terminal portions were confined to the ganglionic layer of the dorsal corpus. No labeled terminals were observed outside the caudal corpus cerebelli. Tracer applications to the dorsal molecular layer resulted in labeled cells not only in the ganglionic layer and the granule cell layer of the dorsal corpus but also in the ganglionic layer of the ventral corpus. The latter finding confirms the presence of intrinsic projections from the ventral region to the dorsal region in the caudal corpus cerebelli. We further revealed that the intrinsic projection neurons are Purkinje cells by immunohistochemistry for zebrin II (aldolase C), which is a marker of Purkinje cells, combined with tracer injections into the dorsal corpus. Unlike injections into the ventral corpus, injections into the dorsal corpus resulted in labeled terminals in extracerebellar structures, such as the nucleus of the medial longitudinal fascicle and reticular formation. The present study suggests that indirect inputs from different telencephalic parts received and processed by distinct regions of caudal corpus cerebelli are sent out of the corpus through the efferent neurons in the dorsal corpus.

DOI： 10.1159/000455962

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Complete spinal transection in adult rats results in poor recovery of hind limb function, whereas significant spontaneous recovery can occur following spinal cord transection in rat neonates. The mechanisms underlying the recovery, however, are poorly understood. Recent studies in rodents suggested that the recovery is not due to axonal regeneration, but rather due to reorganization of the neural circuits in the spinal cord below the injury site, including central pattern generators. Few studies have reported histological evidence for changes in the primary sensory fibers or terminals. Thus, in the present study, we transected spinal cords of rats at thoracic level 8 at postnatal day 5. Four weeks after the injury, biotinylated-dextran amine (BDA), an anterograde tracer, was injected into the dorsal root ganglion of the lumbar spinal cord to examine the localization of sensory fibers and their terminal buttons in the spinal cord. BDA-positive axons in the rat spinal cord following neonatal spinal transection (neo ST) were longer than those in sham-operated or normal rats. The number of terminal buttons was also higher in spinal cords of neo ST rats compared with sham-operated or normal rats. These findings suggest that sensory fibers project more strongly and make more synapses following neo ST to compensate for the lack of supraspinal projections. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2015.07.046

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

BACKGROUND: The descending antinociceptive system (DAS) is thought to play crucial roles in the antinociceptive effect of spinal cord stimulation (SCS), especially through its serotonergic pathway. The nucleus raphe magnus (NRM) in the rostral ventromedial medulla is a major source of serotonin [5-hydroxytryptamine (5-HT)] to the DAS, but the role of the dorsal raphe nucleus (DRN) in the ventral periaqueductal gray matter is still unclear. Moreover, the influence of the noradrenergic pathway is largely unknown. In this study, we evaluated the involvement of these serotonergic and noradrenergic pathways in SCS-induced antinociception by behavioral analysis of spinal nerve-ligated (SNL) rats. We also investigated immunohistochemical changes in the DRN and locus coeruleus (LC), regarded as the adrenergic center of the DAS, and expression changes of synthetic enzymes of 5-HT [tryptophan hydroxylase (TPH)] and norepinephrine [dopamine β-hydroxylase (DβH)] in the spinal dorsal horn. RESULTS: Intrathecally administered methysergide, a 5-HT1- and 5-HT2-receptor antagonist, and idazoxan, an α2-adrenergic receptor antagonist, equally abolished the antinociceptive effect of SCS. The numbers of TPH-positive serotonergic and phosphorylated cyclic AMP response element binding protein (pCREB)-positive neurons and percentage of pCREB-positive serotonergic neurons in the DRN significantly increased after 3-h SCS. Further, the ipsilateral-to-contralateral immunoreactivity ratio of DβH increased in the LC of SNL rats and reached the level seen in naïve rats, even though the number of pCREB-positive neurons in the LC was unchanged by SNL and SCS. Moreover, 3-h SCS did not increase the expression levels of TPH and DβH in the spinal dorsal horn. CONCLUSIONS: The serotonergic and noradrenergic pathways of the DAS are involved in the antinociceptive effect of SCS, but activation of the DRN might primarily be responsible for this effect, and the LC may have a smaller contribution. SCS does not potentiate the synthetic enzymes of 5HT and norepinephrine in the neuropathic spinal cord.

DOI： 10.1186/s12990-015-0039-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

We used confocal microscopy and immunohistochemistry to characterize the morphology of the subcutaneous neurons and the innervation of the slime glands and striated muscles in the hagfish Myxine glutinosa. A rich plexus of 5HT-, ChAT- and TH-positive neurons is described in the capsule of the slime glands. These neurons, like those of the subcutaneous plexus, receive pericellular terminations from the axons of central cells. Capsular neurons receive innervation from 5HT-positive and nNOS-positive nerve fibres. Other nerve endings belonging to two separate nerve populations are identified in the striated muscles. They contain TH and nNOS immunoreactivity. Due to the lack of any topographical labelling, the cell origin and the projections of the neurons into the cranial and spinal nerves are unknown. This study provides anatomical evidence of multiple (5HT and nNOS) peripheral innervation of the neurons. However, it does not provide information about the function of these neurons in the hagfish. We suggest that hagfish neurons have a phylogenetic relationship with the spinal group of the dorsal cells of lampreys and the supramedullary cells of teleosts.

DOI： 10.1111/azo.12068

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Spontaneous nerve regeneration beyond the scar frequently occurs in fish after spinal cord lesions, in contrast to mammals. Here we examined the spatiotemporal relationship between the fibrous scar and axonal regeneration in the goldfish. Within 1 week after hemisection of the spinal cord, the open wound was closed by a fibrous scar that was demarcated from the surrounding nervous tissue by the glia limitans, which was immunoreactive for laminin. Within 1 week after hemisection, regenerating axons entered the fibrous scar, and were surrounded by laminin-coated tubular structures continuous with the glia limitans. Regenerating axons that initially entered the fibrous scar were usually accompanied by glial processes. Within 2-3 weeks after hemisection, the tubular structures became enlarged, and the regenerating axons increased in number, fasciculating in the tubules. Glial processes immunoreactive for glial fibrillary acid protein and 5-hydroxytryptamine neurons then entered the tubular structures to associate with the regenerating axons. The tubular structures developed further, creating tunnels that penetrated the fibrous scar, through which the regenerating axons passed. At 6-12 weeks after hemisection, the fibrous scar was smaller and the enlarged tunnels contained many glial processes and several axons. The findings of present study demonstrated that, following spinal lesions in goldfish, regenerating axons enter and pass the scar tissue. The regenerating axons first enter the fibrous scar with glial elements and then grow through laminin-coated tubular structures within the fibrous scar. Invasion by glial processes and neuronal elements into the tubular structures reduces the fibrous scar area and allows for more regenerating axons to pass beyond the fibrous scar. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2014.09.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The mechanisms underlying paclitaxel-induced peripheral neuropathy remain unknown. Nerve growth factor (NGF) is a representative neurotrophic factor that maintains neuronal function, promotes survival, and mediates neuropathic pain. We investigated expression levels of NGF and its receptors in the dorsal root ganglia (DRG) and spinal dorsal horn (DH) following paclitaxel treatment. Intraperitoneal (I.P.) administration of paclitaxel induced significant mechanical hypersensitivity and cold allodynia in rats, significantly increased the expression of NGF and its receptor tyrosine kinase receptor A (trkA) in the DRG, and increased NGF expression in the DH. In contrast, paclitaxel treatment did not alter the mRNA levels of NGF or its receptors in the DRG, DH, sciatic nerve, or hindpaw skin. Moreover, expression of NEDD4-2, a negative regulator of trkA, was significantly increased in the DRG of paclitaxel-treated rats. Intrathecal (I.T.) administration of the tyrosine kinase receptor inhibitor k252a significantly alleviated mechanical hypersensitivity in paclitaxel-treated rats. Our results suggest that NGF-trkA signaling is involved in mechanical allodynia in paclitaxel-induced neuropathy.

DOI： 10.1016/j.bbrc.2014.01.082

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

It is well recognized that a juvenile brain is more plastic than an adult brain and often undergoes better functional recovery following cortical injury. Infants treated with hemispherectomy to cure intractable epilepsy often exhibit restored normal motor function in the extremities contralateral to the lesion. Neuronal mechanisms of functional recovery after such a large cortical damage at a young age have been studied using animals with a similar lesion, hemidecortication. In such animals, descending pathways from the undamaged sensorimotor cortex to the ipsilateral forelimb motoneurons are reorganized as restoring normal motor function of the forelimb contralateral to the injury. Similar aberrant pathways from the motor cortex to the ipsilateral motoneurons are also generated following suppression of cortical activity in the other hemisphere, suggesting the development of contralateral connections in an activity-dependent manner in normal animals. Thus, formation of ipsilateral descending pathways following neonatal hemidecortication might be due to a loss of balance in cortical activity between the two hemispheres. Studies using animal models of neonatal cortical injury can reveal mechanisms of neural development and may help to establish therapeutic strategies to facilitate recovery from human juvenile cortical injury.

DOI： 10.1016/j.neures.2013.08.011

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18892/jsnas.13.3_219

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本アフェレシス学会  

フィルター無使用で白血球除去装置ポータブル化が可能か,基礎的検討を行った.基礎となる理論は,(1)白血球系細胞は細血管では壁面を転がるように流れる特性を持つこと,(2)細管では液体は中心流や壁流などの層流を形成して流れ,中心流は回路抵抗が低いこと,(3)白血球の様な自走能を持つ細胞は極めて細い繊維に寄り添うように付着する接触走性の特性を持つこと,である.平均内径3mmの血液回路の一部に断面直径3.3μの極細ポリエステル繊維UFPFsと通常の太さ16μのポリエステル繊維RPFsの2種類の筒状布帛を配置し,白血球系細胞が回路壁面で繊維に捕捉される設計とした.ヘパリン化した犬を用いた血液ポンプ無使用の静脈-静脈回路2時間では160ml/minの血流量を維持し,UFPFsの白血球捕捉数はRPFsの5倍強であった.この結果はUFPFsを用いた回路壁面白血球捕捉法は効果的であり,その手法を用いた装置ポータブル化の可能性を示唆している.

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その他リンク： http://id.nii.ac.jp/1141/00152217/

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AIM: Recently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism. METHODS: We used four kinds of cells for this experiment; full-length genome HCV RNA replicon cells (OR6), sub-genomic HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon-α. The triglyceride (TG) levels in the lipoprotein subclasses of the culture medium were measured by high-performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using the in vitro system, liver biopsy samples obtained from the patients were also examined. RESULTS: The content of TG in the large low-density lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than in the OR6c cells (P < 0.01). Examination of the HTGL expression levels in the patients' livers revealed a decrease in HTGL expression in the chronic hepatitis C liver as compared with that in the chronic hepatitis B or non-alcoholic steatohepatitis liver (P < 0.01). CONCLUSION: We showed that HCV inhibits HTGL production in hepatocytes, inducing a change of the lipoprotein profile.

DOI： 10.1111/hepr.12072

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

OBJECT: Entrapment of the superior cluneal nerve (SCN) in an osteofibrous tunnel in the space surrounded by the iliac crest and the thoracolumbar fascia is a cause of low-back pain (LBP). Several anatomical and surgical reports describe SCN entrapment as a cause of LBP, and a recent clinical study reported that patients with suspected SCN disorder constitute approximately 10% of the patients suffering from LBP and/or leg symptoms. However, a detailed anatomical study of SCN entrapment is rare. The purpose of this study was to investigate the courses of SCN branches and to ascertain the frequency of SCN entrapment. METHODS: Branches of the SCN were dissected in 109 usable specimens (54 on the right side and 55 on the left side) obtained in 59 formalin-preserved cadavers (average age at death 84.8 years old). All branches were exposed at the points where they perforated the thoracolumbar fascia. The presence or absence of an osteofibrous tunnel was ascertained and, if present, the entrapment of the branches in the tunnel was determined. RESULTS: Of 109 specimens, 61 (56%) had at least 1 branch running through an osteofibrous tunnel. Forty-two medial (39%), 30 intermediate (28%), and 14 lateral (13%) SCN branches passed through such a tunnel. Of these, only 2 medial branches had obvious entrapment in an osteofibrous tunnel. There were several patterns for the SCN course through the tunnel: medial branch only (n = 25), intermediate branch only (n = 11), lateral branch only (n = 4), medial and intermediate branches (n = 11), medial and lateral branches (n = 2), intermediate and lateral branches (n = 4), and all branches (n = 4). CONCLUSIONS: Several anatomical variations of the running patterns of SCN branches were detected. Entrapment was seen only in the medial branches. Although obvious entrapment of the SCN is rare, it may cause LBP.

DOI： 10.3171/2013.4.SPINE12683

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

BACKGROUND: Hepatitis C virus (HCV) induces endoplasmic reticulum (ER) stress which, in turn, activates the unfolding protein response (UPR). UPR activates three distinct signalling pathways. Additionally, UPR induces autophagy (UPR-autophagy pathways). On the other hand, it has become clear that some positive-single-strand RNA viruses utilize autophagy. Some groups have used the siRNA silencing approach to show that autophagy is required for HCV RNA replication. However, the mechanism of induction of the UPR-autophagy pathways remain unclear in the cells with HCV. METHOD AND RESULTS: we used a genome-length HCV RNA (strain O of genotype 1b) replication system (OR6) in hepatoma cells (HuH-7-derived OR6 cells). As control, we used OR6c cells from which the HCV genome had been removed by treatment with interferon-α. The UPR-autophagy pathways were activated to a greater degree in the OR6 cells as compared to the OR6c cells. Rapamycin, mTOR-independent autophagy inducer, activated HCV replication in the OR6 cells. On the other hand, HCV replication in the cells was inhibited by 3-methyladenine (3-MA), which is an inhibitor of autophagy. Salubrinal (Eukaryotic Initiation Factor 2(eIF2)-alpha phosphatase inhibitor), 3-ethoxy-5, 6-dibromosalicylaldehyde (X-box binding protein-1 (XBP-1) splicing inhibitor) and sp600125 (c-Jun N-terminal kinases (JNK) inhibitor) inhibited HCV replication and autophagy. Additionally, HCV replication and autophagy were inhibited more strongly by combination of these inhibitors. CONCLUSION: Our results suggest that UPR-autophagy pathways exert an influence on HCV replication. Therefore, control these pathways may serve as a novel therapeutic strategy against replication of HCV.

DOI： 10.1016/j.bbrc.2013.01.103

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tract tracing is a fundamental technique in neuroanatomy for examining fiber connections in the nervous system. After the introduction of horseradish peroxidase 40 years ago, many tracing substances have been used for neuroanatomical studies on various nervous systems. Here, we described retrograde tracing techniques using multiple fluorescent tracers, which make it possible to detect axonal collaterals. This technique is useful to study the development of axonal trajectories, as well as regenerative and compensatory mechanisms of animals that undergo neural damage at early stages.

DOI： 10.1007/978-1-62703-444-9_31

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記述言語：日本語   出版者・発行元：(一社)日本脊椎脊髄病学会  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：公益社団法人日本理学療法士協会  

【緒言】本研究では,生後7日に左大脳皮質傷害を被ったラットにおける経時的な代償反応を逆行性トレーサー法を用いて検討した。【方法】左大脳皮質吸引除去術後2, 3, 4, 5週において右頸髄にFITC-CTB, 左頸髄にFastBlueを注入し,標識された脊髄下行性投射ニューロンの数を正常発達ラットと比較検討した。【結果】FITC-CTBで標識された同側皮質脊髄ニューロンは,全週齢において吸引除去群で有意に多く存在した。二重標識された皮質脊髄ニューロンは両群で確認され,吸引除去群では術後4, 5週において有意に増加した。しかし,その数は数%に過ぎなかった。延髄腹側網様核および延髄縫線核に存在するFITC-CTB標識ニューロンは,術後4, 5週にて吸引除去群で有意に多く存在していた。【結論】新生仔期一側大脳皮質傷害後には,発達過程において淘汰されず残存した皮質ニューロンからの同側性脊髄投射が代償機能の中心的役割を果たし,非傷害側皮質脊髄路軸索からの側枝発芽や,脳幹からの投射も一部関与していることが示唆された。

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The LIM homeodomain protein Islet-1, an embryonic marker for motoneurons in the spinal cord, has been reported to be heterogeneously expressed among motoneuron groups in mouse. In the present study, we examined Islet-1 expression in the thoracic and rostral lumbar spinal cord in prenatal mice. In the thoracic spinal cord at embryonic day 12.5 (E12.5) and E13.5, strong Islet-1 immunoreactivity was observed in the lateral group of the ventral horn, whereas weaker immunoreactivity was observed in the ventral group. Strong Islet-1 immunoreactivity was also observed in the intermediolateral area and more medial part of the intermediate zone. In the rostral lumbar spinal cord at E12.5 and E13.5, strong Islet-1 immunoreactivity was observed in the lateral group of the ventral horn, and in the intermediolateral nucleus, whereas weaker immunoreactivity was observed in the ventral, and dorsolateral groups. At E14.5, the number of Islet-1 immunoreactive neurons was reduced in the spinal cord, but the distribution pattern was similar to that at E12.5 and E13.5. At E15.5, Islet-1 immunoreactivity was almost completely confined to the intermediolateral area. Some weakly immunoreactive neurons were observed in the ventral horn. The findings of the present study indicated that Islet-1 expression at embryonic stages differs among the motoneuron groups in the thoracic and rostral lumbar spinal cord. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ijdevneu.2011.05.007

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：F HERNANDEZ  

Immunoglobulin-positive lymphocytes are present close to vasoactive intestinal polypeptide-positive (VIP(+)) nerve fibers in the lamina propria of the intestinal tract, and have an important role in mucosal defense. The number of immunoglobulin A-positive (IgA(+)) cells close to the epithelial basement membrane and nerve fibers is increased by the administration of lipopolysaccharides, which induce IgA secretion into the intestinal lumen. The relationship between immunoglobulin-positive lymphocytes and the VIP(+) nerve fibers during inflammation, such as in inflammatory bowel disease, however, is not well known. The morphological relationship between immunoglobulin-positive cells and the basement membrane or the VIP(+) nerve fibers in the colon was examined using double immunofluorescent labeling in an inflammatory bowel disease mouse model created by oral administration of dextran sodium sulfate (DSS). DSS administration induced goblet cell loss, crypt loss, intestinal epithelium deformation and infiltration of inflammatory cells in the mucosa. In the colon, the number and percentage of IgA(+) lymphocytes close to the basement membrane and the VIP(+) nerve fibers in the lamina propria increased after DSS administration, in parallel with the pathologic progress in the inflamed tissue. On the other hand, the percentage of immunoglobulin G-positive (IgG(+)) lymphocytes close to the basement membrane and the VIP(+) nerve fibers decreased, although the total number of IgG(+) lymphocytes in the lamina propria increased. We suggest that the immunoglobulin-producing lymphocytes and enteric nerve fibers in the colon normally have a close morphological relationship, and that this relationship is reinforced in a cell-specific manner during inflammation.

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本脊椎脊髄病学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Semaphorins, one of the repulsive axonal guidance factors during development, are produced under pathological conditions in adult animals. In the neuropathic pain state associated with peripheral nerve injury, synaptic reorganization occurs in spinal cord dorsal horn. In the present study, we investigated the roles of intrathecal administration of Sema3A, a secreted semaphorin, in the spinal cord of chronic constriction injury (CCI) model rat. Neuropilin 1 (NPR1) and Plexin A (PlexA), co-receptors of Sema3A, were expressed in the dorsal horn of naive rats. NPR1, and not PlexA, protein expression increased in the dorsal spinal cord of CCI rats. Recombinant Sema3A protein attenuated mechanical allodynia and heat hyperalgesia in CCI rats, whereas heat-inactivated Sema3A had no effect. Immunohistochemistry revealed that Sema3A partially restored the decrease of isolectin B4-positive unmyelinated nerve terminals in lamina II of the ipsilateral dorsal horn of CCI rats. Contrary to our expectations. Sema3A did not change the distribution of myelinated fibers in lamina II at 7 days after CCI. Those results suggested that the suppressive role for Sema3A in the development of neuropathic pain associated with peripheral nerve injury in adult rats, which seemed to be independent from prevention of the myelinated fiber sprouting into lamina II. (C) 2010 Elsevier Ireland Ltd and the japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2010.09.006

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

To examine the compensatory mechanisms in rats that underwent left decortication at postnatal day 7 (P7), we injected the retrograde tracers fluorescein isothiocyanate-cholera toxin B subunit (FITC-CTB) and Fast Blue (FB) into the right and left upper cervical spinal cord, respectively, at postoperative weeks 2, 3, 4, and 5 and counted the number of retrogradely labeled corticospinal neurons in the right cerebral cortex compared with that in normally developed rats. Significantly more ipsilaterally projecting neurons were labeled with FITC-CTB in the decorticated rats compared with normal rats at all time points examined. The number of labeled neurons was similar to that at P7 in normal rats. There were also some FITC-CTB and FB double-labeled neurons in both decorticated and normal rats. The number of double-labeled neurons in the decorticated rats increased each week and was significantly greater than that in normal rats at postoperative weeks 4 and 5. The present results suggest that the elimination of ipsilaterally projecting axons observed in normal rats was prevented in the decorticated rats, so that the cerebral cortex neurons on the unlesioned side projected corticospinal tracts to the ipsilateral spinal cord. Furthermore, the collaterals of the corticospinal tracts originating from the cerebral cortex on the unlesioned side also project to the ipsilateral spinal cord. These compensatory mechanisms might underlie the acquisition of motor function in these animals.

DOI： 10.1159/000335526

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Onuf&apos;s nucleus in the lumbosacral spinal cord, comprising somatic motoneurons that innervate the pelvic floor muscles via the pudendal nerve, shares some characteristics with the autonomic preganglionic neurons and functions in coordination with the autonomic nervous system. In mouse, neurons projecting to the urethral sphincter and ischiocavernosus muscles form the dorsolateral (DL) nucleus at the caudal lumbar levels, whereas neurons projecting to the limb and hip joint muscles comprise the retrodorsolateral and ventral nucleus, as well as the DL nucleus at the rostral lumbar levels. The results of the present study in mouse revealed that the expression pattern of a LIM homeodomein protein Islet-1, an embryonic marker for motoneurons in the spinal cord, was different among motoneuronal groups at the prenatal stage (embryonic days 13.5-15.5); the highest expression was observed in the DL at the caudal lumbar cord, whereas there was little expression in the lateral part of the rostral DL. Islet-1 expression was also observed in the parasympathetic preganglionic neurons at the sacral spinal cord. These findings provide evidence that the DL neurons at the caudal lumbar cord, corresponding to Onuf&apos;s nucleus, are chemically distinct among the motoneuronal groups at the prenatal stages. This differential Islet-1 expression among the motoneuronal groups suggests that Islet-1 not only leads to a motoneuronal lineage, but also to the differentiation of motoneuronal subsets in the lumbosacral spinal cord. (C) 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2009.02.020

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

The sympathetic preganglionic cell pool in Xenopus laevis can be divided into four parts, i.e., the intercalated nucleus (IC) and the intermediolateral nucleus (IML) located respectively at the medial and the lateral borders of the lateral field, the lateral funiculus, and the ventral field within the thoracolumbar spinal segments. We compared the location of the preganglionic cells labeled following tracer application to the paravertebral sympathetic chain with those labeled following application to the celiac ganglion (CG), the adrenal gland (AG), and the splanchnic nerves (SNs) and found that their relative contribution differs depending on the sites. In tracer application to the paravertebral chain ganglia and the sympathetic trunk, 31.4-41.9% and 43.9-58.4% of labeled cells were detected respectively in the IC and in the IML, whereas application to the CG, AG, and on all the SNs, revealed that more than 84% of labeled cells were found in the IML and in the lateral funiculus with less than 8.6% in the IC. The contribution of the ventral field cells was less than 7.5% in all experiments. This type of topographic cytoarchitecture is a character shared with the mammalian preganglionic cell pool, but what distinguishes it from that of mammals is its systematic form throughout the entire longitudinal extent of the pool. In Xenopus, differences of mean soma areas and dendritic projections of labeled cells also suggest that the cell pools are distinguished not only by their location and axonal projections, but also by the morphology of their cells. J. Comp. Neurol. 513:292-314, 2009. (C) 2009 Wiley-Liss, Inc.

DOI： 10.1002/cne.21956

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

A tyrosine hydroxylase-immunoreactive cell mass is found in the caudal portion of the dorsal nerve ganglion of the red-eared slider, Trachemys scripta elegans. The ganglion appears as a flat oval structure in the horizontal plane, where the major axis runs latero-medially, and the minor axis rostro-caudally in the ventral view. A communicating branch to the sympathetic chain diverges from the top of each tubercle which lies on the caudo-lateral side of the ganglion. A tyrosine hydroxylase-immunoreactive cell mass is located in this tubercle. This cell mass exists in both sexes. Tyrosine hydroxylase-immunoreactive cells, that contain Nissl bodies in cytoplasm and are enveloped by the satellite cells, are multipolar and their neural processes are distributed in a distal direction into the spinal nerve. The range of distribution of the synapsin Immunoreactive structures is limited to the tyrosine hydroxylase-immunoreactive cell mass. The chelonian dorsal spinal nerve ganglia are a conglomerate of the spinal nerve ganglion proper and the sympathetic ganglion. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000219486

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. Plaque hemorrhage in carotid atherosclerosis promotes plaque progression, resulting in cerebrovascular disease. Hypoxia inducible factor-1 alpha (HIF-1 alpha) induces angiogenesis via the expression of vascular endothelial growth factor (VEGF) and E26 transformation-specific-1 (Ets-1). The authors investigated human carotid plaques to determine whether these hypoxia-inducible angiogenic proteins play a major role in intraplaque angiogenesis and hemorrhage.
Methods. The expression of HIF-1 alpha, VEGF, and Ets-1 was analyzed using immunohistochemistry and Western blotting in 29 human carotid plaques obtained at carotid endarterectomy. The authors investigated the relationship between plaque characteristics and clinical symptoms.
Results. A higher incidence of plaque hemorrhage was observed in plaques associated with symptoms than in those without symptoms (p = 0.03). Hypoxia-inducible factor-1 alpha, VEGF, and Ets-1 coexisted in the deep layer of plaque, where angiogenesis was remarkably developed; the expression levels of HIF-1 alpha, VEGF, and Ets-1 were significantly enhanced in the main lesion of the plaque (p &lt; 0.01). Symptomatic plaques showed higher expression of VEGF (p = 0.04) than asymptomatic plaques. Plaques with hemorrhage showed a higher incidence of plaque ulcer (p = 0.001) and higher expression of Ets-1 (p = 0.03) than those without hemorrhage. Moreover, significantly increased expressions of VEGF (p = 0.01) and Ets-1 (p = 0.006) were observed in plaques with not only hemorrhages but also ulcers and severe stenosis.
Conclusions. The findings in this study suggest that hypoxia-inducible angiogenic proteins in human carotid atherosclerosis promote intraplaque angiogenesis, which can induce plaque hemorrhage and progression.

DOI： 10.3171/JNS/2008/109/7/0083

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Farnesol is known as a quorum-sensing molecule for Candida albicans and is recognized to play pathogenic roles in Candida infection. To assess the possible role of farnesol in mucosal C. albicans infection, the effects of farnesol treatment against experimental oral candidiasis in mice were examined. Prednisolone-pretreated ICR mice were orally infected with C. albicans and 3, 24 and 30 hr later the animals were orally given farnesol. Forty-eight hr later they were killed for observation. Farnesol treatment in a dose ranging between 1.125 and 9 mu mol/mouse showed a protective effect against oral candidiasis in a dose-dependent manner, at least as estimated by symptom scores of tongues. At 9 mu mol/mouse it decreased bodyweight loss. Histological studies of 2.25 mu mol/mouse farnesol-treated animals indicated that farnesol suppressed mycelial growth of C. albicans on the surface of tongues, but microbiological study did not prevent the change of CFU of C. albicans cells not only on tongues but also in feces, kidneys and livers. These results suggest that farnesol has very characteristic roles in protection against mucosal candidiasis.

DOI： 10.1111/j.1348-0421.2008.00044.x

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Immunoglobulin A (IgA) lymphocytes are present close to the nerve fibers in the lamina propria of the small intestine, and the administration of lipopolysaccharides (LPSs) increases the number of these cells and IgA secretion to the lumen. In the present study, we demonstrated that the nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) were close to the IgA lymphocytes in the mouse ileum lamina propria. Three hours after intraperitoneal administration of LPSs, IgA lymphocytes close to VIP nerve fibers, those close to basement membrane, and those close to both VIP nerve fibers and basement membrane were increased in number. Further, all IgA lymphocytes seen in the ileum lamina propria expressed the receptors for VIP, VIPR1, and VIPR2. Electron microscopy revealed that varicosities were in close apposition to the lymphocyte plasma membrane. The present study suggests that VIP/NPY/CGRP neurons in the submucosal plexus have a close anatomical relationship to IgA lymphocytes, playing a role in the secretion of IgA and intestinal fluid in response to stimulation by lipopolysaccharides, pathogens, or toxins. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbi.2007.08.013

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

In contrast to mammals, spontaneous nerve regeneration occurs in the teleost spinal cord. In the present study, we examined whether neurogenesis is involved in posttraumatic regeneration in the goldfish spinal cord. In intact fish, many spinal cells positive for both a monoclonal neuronal marker (Hu) and bromodeoxyuridine (BrdU) were observed 24 h after i.p. injection of BrdU, suggesting that constant neurogenesis occurs in the goldfish spinal cord. After hemisection of the spinal cord, the number of spinal cells positive for Hu and BrdU was significantly increased around the lesion site. The number of Hu- and BrdU-positive cells reached the maximum level 7 days after hemisection. In intact fish, spinal cells positive for both Hu and BrdU were also observed 5 weeks after BrdU injection, suggesting that newborn neurons survive for a long time. Six weeks after hemisection, the number of surviving Hu- and BrdU-positive cells at the lesion site was significantly increased as compared with that in intact fish, and some of them were also positive for 5-HT. A retrograde tract tracing study showed that the 5-HT+ neurons were close to the regenerated axons passing through the lesion site. These results suggest that adult neurogenesis occurs in the goldfish spinal cord, and that neurogenesis is activated by spinal cord lesion. The newly produced neurons survive a long time at the lesion site, and might participate in the repair of injured tissue and in the regeneration of descending long axons beyond the lesion site. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2007.10.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

We analyzed the morphologic and microbiologic aspects of the process of adhesion and invasion in the early stages of Candida albicans oral infection in a murine system. ICR mice were anesthetized by intramuscular injection with chlorpromazine chloride and then orally inoculated by swabbing with the C. albicans yeast cells. Their tongues were resected 1-3 h after inoculation, washed sequentially with a physiological saline and 0.25% trypsin-solution and then homogenized. The number of viable C. albicans cells on the tongue surface was counted and fround to increase from 1-3 h after inoculation. Most of the Candida cells attached to the tongue surface were present in clusters, mainly located in the gaps between lingual papillae and were covered with a mucoidal substance. By 3 h after inoculation, these clusters frequently formed mycelia and could not be easily detached from the tongue surface by trypsin treatment. Observation of SEM and histological sections stained by Fungiflora Y revealed that the Candida hyphae at 3 h stretched out of the cluster and entered the tongues through the surface. These results indicate that Candida hyphae begin to invade the tongue surface within 3 h after inoculation and suggest that the mucus-like substance covering these cells may have an important early role in the interaction between the Candida cells and the tongue mucosal epithelium.

DOI： 10.1080/13693780802039919

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Following spinal transection, descending spinal projections from goldfish brainstem neurons spontaneously regenerate beyond the lesion site. The nucleus of the medial longitudinal fasciculus (nFLM), which has a critical role in swimming, also sends regenerated axons over a long distance to the ipsilateral spinal cord. To examine whether regenerated axons rie-innervate the appropriate targets, we injected rhodamine dextran amine (RDA) into the nFLM of spinally transected goldfish and examined anterogradely labeled axons in the spinal cord. In intact controls, there were many RDA-labeled boutons or varicosities in the spinal cord in close apposition to both neurons positive for calcitonin gene-related peptide (CGRP), and those negative for CGRP. This suggests that the nFLM neurons project axons directly to the motoneurons and interneurons in the spinal cord. Four days after hemisection 1 mm caudal to the rostral. end of the spinal cord, the number of RDA-labeled boutons in close apposition to the spinal neurons was significantly decreased on the side ipsilateral to the injection. Six to twelve weeks after spinal hemisection, regenerated axons ran through the repaired lesion site, and the number of RDA-labeled boutons or varicosities in close apposition to the ipsilateral spinal neurons had returned to the control level. These findings suggest that the midbrain-spinal pathway, critical for locomotion in fish, spontaneously regenerates beyond the lesion site to re-innervate the appropriately innervated targets after spinal lesion. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2007.04.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Objective: In the past the microkinetics of blood flow in the infrared pit organs of pit: vipers has been studied with Doppler flowmetry using various infrared stimuli such as a human hand or soldering iron at various distances; lasers of various wavelengths, etc. Quick-acting variations in blood flow were recorded; and interpreted as a cooling mechanism for avoiding afterimage in the infrared receptors. However; the Doppler measurements provided only the summation of Blood flow in a number of vessels covered by the sensing probe; big did not: give data on flow in individual vessels.
Methods: In the present: work the authors introduced into the bloodstream of Gloydius and Trimeresurus pit vipers fluorescent microspheres labeled with fluorescein isothiocyanate (FITC) contained in a solution of FITC-dextran in physiological saline. They observed the passage of the microspheres through individual pit organ vessels with a fluorescent microscope to which was attached a high-speed video camera and image intensifier. Output of the camera was recorded before., during; and after stimulus with a 810-nm diode laser. Recording was done at 2.50 frames/s on high-speed video apparatus and downloaded to a hard disk. Disk files were loaded into proprietary software and particles were tracked and average velocities calculated. The data were then tested for significance by ANOVA with post hoc tests.
Results: A significant (p &lt; .05) increase in blood velocity was found at the focal point of the stimulus laser; but not anywhere removed from this point. Proximal severing of the pit sensory nerves caused degeneration of the pit receptor terminals and abolished stimulus-induced blood flog changes; bat did not affect normal blood flow.
Conclusions: The authors conclude that: the receptors themselves are directly and locally controlling the smooth muscle elements of the blood vessels; in response to heating of the receptors by infrared radiation. They speculate that the heavy vascularization constitutes a cooling system for the radiation-encoding receptors, and farther that the agent of control may be a volatile neuromediator such as nitric oxide.

DOI： 10.1080/10739680601131184

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

The sympathetic nervous system develops as an evolutionary trait with gnathostomes ( jawed vertebrates), but not with agnathan fishes (i.e., hagfishes and lampreys). Organization of the sympathetic preganglionic neuronal columns is different in teleosts and anurans. In the teleosts so far examined, the majority of sympathetic preganglionic neurons (SPNs) are located in the dorsal part of the spinal central gray matter. In Tetraodontiformes, the cell column occupies only two rostral spinal segments, which are distinct in their cytoarchitecture and projections. On the other hand, the SPNs of anurans form two cell columns segregated mediolaterally. The lateral and medial columns are also distinct in their cytoarchitecture and projections. The neuroactive substances expressed in the SPNs both in teleosts and anurans are coded to the projections. In anurans, the SPNs containing gonadotrophin-releasing hormone and those containing calcitonin gene-related peptide are involved in the regulation of blood vessels and cutaneous glands, respectively. In the file-fish, the SPNs containing galanin project specifically to nonadrenergic non-cholinergic postganglionic neurons in the cranial sympathetic ganglia. Therefore, both anuran and teleost systems have different morphological and chemical-coded patterns for functional variation, although the anuran sympathetic nervous system has more organizational similarity with that of amniotes. Copyright (c) 2007 S. Karger AG, Basel.

DOI： 10.1159/000095199

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

The visceral reflexes of the pelvic organs are mediated by connections between primary afferents innervating the pelvic organs and parasympathetic preganglionic neurons in the intermediolateral column of the sacral spinal cord. The present immunohistochemical study revealed many varicosities expressing transient receptor potential vanilloid 1 (TRPV1) that were closely apposed to the preganglionic neuronal perikarya at embryonic day 16 in mice. Many, but not all, varicosities expressing TRPV1 in the intermediolateral column were also immunopositive for calcitonin gene-related peptide. In contrast, no nerve fibers expressing TRPV1 projected to the sympathetic preganglionic cell column in the lumbar spinal cord in prenatal stages. The results of the present study raised the possibility that the primary afferents transmit signals elicited by the activation of TRPV1 receptors to the sacral parasympathetic preganglionic neurons. Thus, the functional circuit for pelvic spinal reflexes, such as micturition induced by urine influx, might develop in the prenatal stages in mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2006.08.067

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

We examined transient receptor potential (TRP) V1 and TRPV2 expression in calcitonin gene-related peptide (CGRP) positive (+) primary sensory neurons projecting to the skin and skeletal muscles of the rat dorsum. Among the dorsal root ganglia at the levels from C2 to Th1, 34.9% of neurons projecting to the skin were positive for CGRP, and 32.6% or 21.6% of neurons projecting to the trapezius muscle or the longissimus muscle were positive for CGRP. Of the small CGRP+ neurons projecting to the skin, 53.5% were positive for TRPV1, 11.6% were positive for TRPV2. Of the small CGRP+ neurons projecting to the trapezius or the longissimus, 53.1 or 53.2% were positive for TRPV1, 8.8 or 8.3% were positive for TRPV2, respectively. In the periphery, 29.3% of CGRP+ nerve fibers were positive for TRPV1 in the skin, whereas 65.0 or 59.8% were positive in the trapezius or the longissimus. Therefore, the present study showed that the percentage of CGRP+ neurons projecting to the trapezius is higher than that to the longissimus, and that the co-localization percentage of CGRP and TRPV1 on the sensory nerves was also higher in the trapezius than in the longissimus and the skin.

DOI： 10.1007/s00418-006-0167-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

Voltage-dependent Ca2+ channels (VDCCs), which consist of multiple subtypes, regulate vascular tone in developing arterial smooth muscle, including the ductus arteriosus (DA). First, we examined the expression of VDCC subunits in the Wistar rat DA during development. Among alpha(1)-subunits, alpha(1C) and alpha(1G) were the most predominant isoforms. Maternal administration of vitamin A significantly increased alpha(1C)- and alpha(1G) transcripts. Second, we examined the effect of VDCC subunits on proliferation of DA smooth muscle cells. We found that 1 mu M nitrendipine (an L-type Ca2+ channel blocker) and kurtoxin (a T-type Ca2+ channel blocker) significantly decreased [H-3] thymidine incorporation and that 3 mu M efonidipine (an L- and T-type Ca2+ channel blocker) further decreased [H-3] thymidine incorporation, suggesting that L- and T-type Ca2+ channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the alpha(1C)-isoform was highly expressed in the neointimal cushion of the DA, where proliferating and migrating smooth muscle cells are abundant. The basic channel properties of the spliced variant did not differ from those of the conventional alpha(1C)-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, alpha(1C)- and alpha(1G)-subunits were predominant in the DA. A novel spliced variant of the alpha(1C)-subunit gene may play a distinct role in neointimal cushion formation in the DA.

DOI： 10.1152/ajpheart.00100.2004

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

In mouse ontogeny, neurons immunoreactive for transient receptor potential vanilloid receptor 1 (TRPV1) were observed primarily in the dorsal root ganglia (DRG) at embryonic day 13 (E13). In the embryonic period, the number of TRPV1(+) neurons decreased, but then gradually increased postnatally. Some of TRPV1(+) neurons were also immunoreactive for calcitonin gene-related peptide (CGRP). At postnatal day 7 (P7), 66% of CGRP(+) neurons were TRPV1(+), and 55% of TRPV1(+) neurons were also CGRP(+) in the L4 DRG. In the peripheral organs, TRPV1-immunoreactive nerve fibers were transiently observed in the skin at E14. They were also observed in the urinary tract at E14, and in the rectum at E15. Many TRPV1(+) nerve fibers in these organs were also CGRP(+). At P1, TRPV1(+) nerve fibers were observed in the respiratory organs, and to a lesser extent in the stomach, colon, skin, and skeletal muscles. The number of TRPV1(+) nerve fibers on each organ gradually increased postnatally. At P7, TRPV1(+) nerve fibers were also observed in the small intestine and kidneys. The percentage of total TRPV1(+) nerve fibers that co-localized with CGRP was greater in most organs at P7 than at P1. The present results indicate that TRPV1 expression on peripheral processes differs among organs. The differential time course of TRPV1 expression in the cell bodies might be related to the organs to which they project. Co-localization of TRPV1 with CGRP on nerve fibers also varies among organs. This suggests that the TRPV1-mediated neuropeptide release that occurs in certain pathophysiologic conditions also varies among organs.

DOI： 10.1007/s00441-005-0013-3

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

To investigate the relation between the enteric nervous system and immunocytes, fecal immunoglobulin (Ig) A and the distribution of IgA-positive cells close to nerve fibers in the lamina propria around the crypts of the small intestine were examined after intraperitoneal injection of lipopolysaccharides (LPS). In mice, IgA in the feces 1 h (LPS1) and 6 h (LPS6) after LPS injection increased compared to that in the control group. In the ileum lamina propria of the LPS1 group, the number of IgA-positive cells close to the epithelial basement membrane was increased. In the LPS6 group, on the other hand, there was a significant increase in the number of IgA-positive cells close to both the basement membrane and the nerve fibers. Our data suggest that LPS induced an increase in the number of IgA-positive cells migrating to the nerve fibers, and that migration to the nerve fibers is as important as migration to the basement membrane for IgA production. &COPY; 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2005.02.047

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

For the purposes of comparative anatomy, we used tracer techniques and immunohistochemistry to study the facial nerve in the pit viper Gloydius brevicaudus and obtained much new data applicable to the function of this nerve in snakes and, in particular, pit vipers. We were able to identify the superior salivatory nucleus in these snakes. Preganglionic fibers from this nucleus pass along the palatine nerve and an anterior communicating branch to reach the pterygopalatine ganglion attached to the deep branch of the trigeminal maxillary nerve. The palatine nerve also contains general somatic afferents and a very few special visceral afferents from some taste buds on the palate. In the mandibular direction, preganglionic fibers from the superior salivatory nucleus join special visceral efferents from the motor nucleus in the hyomandibular nerve, from which they pass into the chorda tympani to course together for a short distance. The special visceral efferents branch off outside the cranium, and the preganglionic fibers continue on to join the trigerninal mandibular nerve to project to small ganglia within the mandible. The chorda tympani also contains general somatic afferents from the mandibular region but no special visceral afferents. This is the first time that the superior salivatory nucleus and its adjuncts have been identified in a snake. The chorda tympani of these snakes is also distinguished from the mammalian condition by lacking any special visceral afferents and by branching outside the cranium. (C) 2004 Wiley-Liss, Inc.

DOI： 10.1002/cne.20081

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

To examine the prenatal development of spinal visceral reflexes, primary sensory nerve fibers immunoreactive for calcitonin gene-related peptide (CGRP) were examined in the spinal cord, particularly in the autonomic preganglionic nuclei of mouse embryos. On embryonic day 16 (E16). CGRP-immunoreactive fibers were first observed in the sacral intermediolateral nucleus (IML) of the parasympathetic division as well as in the lumbar central autonomic nucleus (CA) of the sympathetic division, where they appeared in proximity to preganglionic neuronal perikarya immunoreactive for choline acetyltransferase or nitric oxide synthase. Most of the CGRP-immunoreactive varicosities were negative for substance P. Substance P-immunoreactive varicosities were scattered in these nuclei, but no appositions were seen on the preganglionic neuronal perikarya. On E18, CGRP-immunoreactive fibers were more abundant in the sacral IML and the lumbar CA. Co-expression of substance P and CGRP was frequently observed in the varicosities very close to the preganglionic neuronal perikarya on E18. CGRP-immunoreactive fibers were also observed in the lumbar IML on E18, although significantly fewer were found in this nucleus compared with the sacral IML. In contrast to the upper lumbar level, no fibers immunoreactive for CGRP were observed in the IML at the thoracic level. These results suggest that peptidergic primary sensory fibers grow to project to the selective targets of autonomic preganglionic neurons during the embryonic period. The potential direct connections between the peptidergic primary sensory fibers and preganglionic neurons innervating the pelvic viscera might provide a circuit for spinal visceral reflexes active in embryos. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S0165-3806(03)00165-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Boid snakes have infrared sensing pits that resemble crotaline pits in electrophysiological function and ultrastructure, but differ in gross morphology, number, and location: boids have three or more simple pits in the labial scales vs a single facial pair with more complex morphology in the crotalines. We studied the morphology of the capillary bed and the microkinetics of blood flow in a boid snake, the ball python, Python regius, and compared them with the already known condition in crotalines. We used a Doppler blood flow recorder in conjunction with an electrocardiograph to measure blood flow and heartbeat, and resin casts, transmission electron microscopy, and laser confocal microscopy to study capillary morphology. Blood flow in response to infrared stimulus was virtually identical in the two taxa, but the morphology of the capillary bed differed drastically. In the ball python pits, the capillary bed consisted of a forest of vertically oriented loops with a characteristic dome at the top in contact with the receptor layer of the fundus. Immunohistochemical staining showed pericytes constricting the capillaries and domes with smooth muscle a-actin-labeled processes. Since latency of response was as short as I ms, the capillaries were apparently responding under local control to provide both nutrition and cooling to the heat-sensitive receptors. We concluded that mitochondria-filled receptors provided with a swiftly responding cooling system were nature's most efficient way of attaining infrared imaging. (C) 2003 Elsevier Science (USA). All rights reserved.

DOI： 10.1016/S0026-2862(03)00003-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

The central and peripheral organization of thoracic visceral and somatic nervous elements was studied by applying dextran amines to the proximal cut ends of the thoracic splanchnic and somatic nerves in Xenopus laevis. Many labeled dorsal root ganglion cells of visceral afferents, and all somatic afferents, were located in a single ganglion of one spinal segment, and the two types of cells were distributed topographically within the ganglion. The labeled sympathetic preganglionic neurons were located predominantly in the same area of the thoracic spinal gray as in other frogs and in mammals. The labeled visceral afferents projected to Lissauer's tract and the dorsal funiculus. The visceral fibers of the tract ascended to the level of the subcerebellar area, supplying collateral branches to the lateral one-third of the dorsal horn and to the area of brainstem nuclei, including lateral cervical and descending trigeminal nucleus, and descended to the filum terminale. The visceral fibers of the dorsal funiculus were distributed to the dorsal column nucleus and the solitary tract. A similar longitudinal projection was also seen in the somatic afferents. The dual central pathway of thoracic primary afferents in the anuran spinal cord is a property held in common with mammals, but the widespread rostrocaudal projection through Lissauer's tract may be a characteristic of the anuran central nervous system. In frogs, the direct transmission of primary afferent information to an extremely wide area of the central nervous system may be important for prompt assessment of environmental factors and control of body functions. J. (C) 2003 Wiley-Liss, Inc.

DOI： 10.1002/cne.10514

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100kb around the HLA·B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA·B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

DOI： 10.1034/j.1399-0039.2002.600506.x

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

We compared the distribution of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers of the superficial muscle layer (trapezius muscle), median muscle layer (rhomboideus muscle), and deep muscle layer (longissimus and spinalis muscles) of the dorsum of the rat. SP-and CGRP-immunoreactive fibers were seen along the walls of various types of blood vessels and within nerve bundles in skeletal muscles of all layers. Coexistence of SP and CGRP was evident in nerve fibers along the blood vessel walls. The total number of CGRP varicosities per millimeter square of muscle surface area was evaluated quantitatively, and CGRP varicosities were found to be significantly more numerous in the superficial muscle layer than in the deeper ones. After capsaicin treatment, most of the SP and CGRP fibers along the blood vessel walls were eliminated. These results suggest that sensory nerve fibers containing SP and CGRP are distributed more abundantly in the superficial muscle layer than in the deeper ones and that they might be involved in the regulation of local blood flow. The finding of SP- and CGRP-immunoreactive nerve fibers along the blood vessel walls connecting the trapezius muscle and the hypodermis raises the possibility that sensory stimuli to the skin affect the local blood flow of superficial muscle through collaterals of cutaneous fibers. (C) 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0361-9230(02)00814-6

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

We used transmission electron microscopic montages to examine the composition of nerve bundles serving the infrared pit organs of two species of crotaline snakes, Agkistrodon blomhoffii and A. brevicaudus. In the three main bundles, the myelinated fibers totaled 2,200-3,700, and unmyelinated fibers 2,400. We also discovered for the first time two accessory bundles composed almost entirely of unmyelinated fibers running alongside the main bundles, containing an average total of 3,300 unmyelinated fibers vs. an average of 10 myelinated fibers. Thus, the average total of unmyelinated fibers was nearly twice that of myelinated fibers. To study the nature of the unmyelinated fibers, we did double staining immunohistochemistry with antibodies for substance P (SP) and vasoactive intestinal polypeptide (VIP) in combination with and without capsaicin pretreatment. SP and VIP immunoreactive varicose fibers ran straight toward the center of the pit membrane in parallel with arterioles and venules, and also formed a dense network around the periphery of the membrane. There were three types of fibers: fibers containing only SP, fibers containing only VIP, and fibers containing both peptides. SP-only fibers were distributed singly throughout the pit membrane and in small bundles around the periphery. SP+VIP fibers were distributed sparsely in the pit membrane and around its periphery. VIP-only fibers were distributed throughout the pit membrane and were of smaller diameter than SP and SP+VIP fibers. After treatment with capsaicin, most of the three types of varicose fibers disappeared from the central part of the pit membrane, but those around the periphery remained unaffected. The capsaicin-sensitive fibers may be unmyelinated sensory types, and the unaffected ones may be autonomic nerve fibers.

DOI： 10.1002/cne.10276

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The present study showed neurons immumoreactive for choline acetyltransferase (ChAT) in the cranial sympathetic ganglia lying close to the trigeminal-facial nerve complex of the filefish. In these ganglia, less than 1% of ganglion cells were positive for choline acetyltransferase. Choline acetyltransferase-positive neurons were significantly larger than the randomly sampled neurons in this ganglion. The majority of choline acetyltransferase-positive neurons were negative for tyrosine hydroxylase, but many of them were positive for galanin (GAL). Some neurons were positive for both choline acetyltransferase and tyrosine hydroxylase, but these neurons were rarely immunoreactive for dopamine hydroxylase, suggesting that they are not adrenergic. In the cranial sympathetic ganglia and the celiac ganglia, many nerve fibers immunoreactive for galanin were seen, and varicose terminals were in contact selectively with neurons negative for both choline acetyltransferase and tyrosine hydroxylase, but not with those positive for choline acetyltransferase or tyrosine hydroxylase. Nerve fibers immunoreactive for choline acetyltransferase were found to be present in contact with the deep layer of chromatophores, which was observed only in the labial region. These results suggest that cholinergic postganglionic neurons are present in the filefish cranial sympathetic ganglia, and that they also contain galanin. As few cholinergic sympathetic neurons express tyrosine hydroxylase and none express dopamine hydroxylase, they are unlikely to synthesize noradrenaline or adrenaline. (C) 2002 Elsevier Science B.V All rights reserved.

DOI： 10.1016/S1566-0702(02)00061-9

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

In an immunohistochemical study, the vagal motor nucleus of a teleost, the filefish Stephanolepis cirrhifer, could be divided into a rostral part and a caudal part, and the former into a dorsolateral group and a ventromedial group. The dorsolateral group consisted of neurons immunoreactive for calcitonin gene-related peptide, whereas the ventrolateral-caudal group was negative for calcitonin gene-related peptide. The latter group was retrogradely labeled after dextran amine injection to the visceral ramus of the vagus nerve, suggesting that it is a general visceral efferent column, made up of parasympathetic preganglionic neurons, whereas the dorsolateral rostral group is a special visceral efferent column. In the general visceral efferent column, a dense concentration of nerve fibers immunoreactive for serotonin, tyrosine hydroxylase, cholecystokinin-8, and substance P, and a small number of fibers immunoreactive for neuropeptide Y was observed. Perikarya in contact with varicose terminals immunoreactive for these substances were frequently seen. In contrast, in the special visceral efferent column, only a moderate concentration of neuropeptide Y-immunoreactive nerve fibers and a sparse distribution of fibers immunoreactive for tyrosine hydroxylase were observed. Perikarya in contact with varicose terminals immunoreactive for these substances were rare. These results suggest that the vagal parasympathetic preganglionic neurons might receive multiple inputs of monoaminergic and peptidergic fibers involved in the regulation of the visceral organs. On the other hand, monoaminergic and peptidergic afferent fibers might be of much less significance in the activity of the special visceral efferent component of the vagus nerve. (C) 2002 Wiley-Liss, Inc.

DOI： 10.1002/cne.10238

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Nerve fibers immunoreactive for enzymes synthesizing catecholamines were examined in the central autonomic nucleus, a column of sympathetic preganglionic neurons, in the filefish Stephanolepis cirrhifer. Varicose nerve fibers immunoreactive for tyrosine hydroxylase were densely distributed in the rostral part, sometimes in contact with perikarya but were sparse in the caudal part of this nucleus. Fluorescent double labeling distinguished noradrenergic nerve fibers immunoreactive for both tyrosine hydroxylase and dopamine beta hydroxylase, and dopaminergic fibers immunoreactive only for tyrosine hydroxylase. In the brainstem, catecholaminergic neurons were observed in the locus coeruleus, the caudal dorsomedial reticular zone of the medulla, and the area postrema. Double labeling of tyrosine hydroxylase and dopamine beta hydroxylase showed that the neurons in the locus coeruleus were all noradrenergic, and those in the caudal dorsomedial medulla were mostly noradrenergic, whereas the area postrema contained both noradrenergic and dopaminergic neurons. No catecholaminergic neurons were found in the ventral region of the brainstem. After application of DiI to the central autonomic nucleus, retrogradely labeled neurons were seen in the caudal dorsomedial medulla but not in the locus coeruleus or the area postrema. These findings suggest that the sympathetic preganglionic neurons of the filefish may receive noradrenergic axonal projections from neurons in the caudal dorsomedial medulla, In the light of previous studies, inputs of these catecholaminergic fibers to the central autonomic nucleus may be involved in regulation of sympathetic activity of peripheral organs, together with serotoninergic and peptidergic inputs to this nucleus. J. Comp. Neurol. 442:204-216, 2002. (C) 2001 Wiley-Liss, Inc.

DOI： 10.1002/cne.10082

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

In the cellular column of sympathetic preganglionic neurons (SPNs) of the filefish Stephanolepis cirrhifer, neurons containing galanin (GAL) form a distinct population projecting specifically to non-adrenergic postganglionic neurons in the celiac and cranial sympathetic ganglia. The present study showed that virtually all of the GAL-immunopositive SPNs made contact with many nerve terminals immunopositive for cholecystokinin octapeptide (CCK-8). GAL-negative preganglionic neurons made contact with only 26% of this type of nerve terminal; CCK-8-immunopositive nerve fibers appeared to project selectively to GAL-immunopositive SPNs with projections to specific targets. The CCK-8-positive nerve fibers might be of primary sensory origin, and participate in the visceral reflexes. (C) 2001 Published by Elsevier Science Ireland Ltd.

DOI： 10.1016/S0304-3940(01)02386-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lack of estrogen receptor (ER) results in fluid accumulation and dilation of the efferent ductules, suggesting that the role of estrogen and ER in the male reproductive tract is related to fluid reabsorption in the ductules. In the present study, endocytosis of the nonciliated cells of the efferent ductules was compared morphologically between wild type (WT) and estrogen receptor-α knockout (αERKO) male mice. The epithelial cells lining the WT efferent ductules were tall columnar in shape, whereas those of the αERKO were low columnar. Immunocytochemically, the nonciliated cells of both genotypes showed positive reactions of sulfated glycoprotein-2, but the reaction products were reduced in amount in the αERKO. Electron microscopy revealed that the nonciliated cells of the WT had numerous organelles for endocytosis such as coated pits and vesicles, tubules, endosomes, multivesicular bodies and lysosomes in the apical cytoplasm. These organelles were less developed in the nonciliated cells of the αERKO. Morphometric analysis indicated that there was a significant reduction in area of endocytotic apparatus in the nonciliated cells of the αERKO compared with that of the WT. A tracer study using gold particles demonstrated that the nonciliated cells of both WT and αERKO efferent ductules were capable of taking up luminal contents. These results suggest that reabsorption of the luminal contents via endocytosis takes place in the efferent ductules but is greatly reduced in amount in the absence of ERα. © 2001 Wiley-Liss, Inc.

DOI： 10.1002/ar.1071

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Immunoreactivity for substance P and cholecystokinin-8 was examined in the nerve fibers in the central autonomic nucleus, a cell column for sympathetic preganglionic neurons, in the filefish Stephanolepis cirrhifer. Substance P-immunoreactive fibers were distributed throughout the entire rostrocaudal extent, but were more abundant in the caudal part of the column, where substance P-immunoreactive varicosities sometimes made contacts with the sympathetic preganglionic neurons. Cholecystokinin-8-immunoreactive fibers were found almost entirely in the rostral part of the column, where a dense network of varicosities was in close apposition to a considerable number of the sympathetic preganglionic neurons. Double labeling immunohistochemistry showed that substance P fibers and cholecystokin-8 fibers were entirely different, and distinct from serotonin-immunoreactive fibers. By using immunoelectron microscopy, synaptic specialization was sometimes observed between the dendrites of preganglionic neurons and varicosities immunoreactive for substance P and cholecystokinin-8. Substance P- and cholecystokinin-8 fibers were seen from the descending trigeminal tract, through the dorsolateral funiculus and the ventral portion of the dorsal horn, to the central autonomic nucleus. After colchicine treatment, substance P-immunoreactive perikarya were found in the cranial and spinal sensory ganglia. These results suggest that the sympathetic preganglionic neurons of the filefish receive innervation by substance P fibers and cholecystokinin fibers, and that the former might be of primary sensory origin. Topographical distribution of cholecystokinin-8-immunoreactive terminals in the central autonomic nucleus along the rostrocaudal extent might underlie the differential regulation of sympathetic activity via a distinct population of sympathetic preganglionic neurons. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/1096-9861(20001204)428:1<174::AID-CNE12>3.0.CO;2-U

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

The infrared sensory membranes of pit organs of pit vipers have an extremely rich capillary vasculature that forms many vascular loops, each serving a small number of infrared nerve terminals. We clarified the ultrastructure of capillary pericytes in the pit membranes by scanning and transmission electron microscopy, and examined the immunoreactivity in their cytoplasm to two contractile proteins: smooth muscle alpha -actin (SM alpha -actin) and desmin. The capillary pericytes had two major cytoplasmic processes: thickened primary processes that radiate to embrace the endothelial tube and flattened secondary processes that are distributed widely on the endothelium. Coexpression of SM alpha -actin and desmin was observed in the pericytes of entire capillary segments, and SM alpha -actin was characterized by prominent filament bundles directed mainly at right angles to the capillary long axis. This expression pattern was different from that of capillary pericytes of the scales, where SM alpha -actin was expressed diffusely in the cytoplasm. In a series of electron microscopic sections, we often observed the pericyte processes depressing the endothelial wall. We also observed a close relationship of the pericytes with inter-endothelial cell junctions, and pericyte processes connected with the endothelial cells via gap junctions.
From these findings, we surmised that capillary pericytes in the pit membrane have a close functional relationship with the endothelium, and through their contractile and relaxing activity regulate capillary bloodflow to stabilize production of infrared nerve impulses. Anat Rec 260:299-307, 2000. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/1097-0185(20001101)260:3<299::AID-AR67>3.0.CO;2-V

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The pit organ of pit vipers contains a membrane which serves as an infrared retina, processing infrared information by the degree to which the temperature of trigeminal nerve receptors (terminal nerve masses) is raised. The receptors are arranged in a monolayer array within the pit membrane and irrigated by a capillary network which both supplies energy to the terminal nerve masses and serves as a heat exchange mechanism. This mechanism maintains the receptors at a stable temperature level to increase or decrease their sensitivity and to reduce to a minimum the afterimage effect of a moving stimulus. We used a Doppler laser blood flow meter to measure the local changes in blood flow in response to a point heat source (a small soldering iron) and to direct stimuli (red and infrared lasers). Resection of any one of the trigeminal A-delta fiber trunks innervating the pit membrane abolished blood flow response in the area. innervated, but resection of the main trunk between the primary neurons and the medulla left the response intact. In addition to the A-delta fibers the pit membrane Contains autonomic and sensory C-fiber innervation, but preganglionic resection of parasympathetic neurons, and chemical blocking of postganglionic fibers with atropine and capsaicin had no influence on the blood flow changes. Therefore, on the basis of the rapid response time and the similarity of the blood flow curves to electrophysiological recordings from the receptors, we surmised that all blood flow changes were due to a vasomotor reaction, modulated by the terminal nerve masses directly, resulting in a change in local heat capacity that cools the stimulated receptors back to a basal temperature. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1566-0702(00)00195-8

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Neuropeptides in the motor nerves innervating the red and white muscles of the goldfish Carassius auratus were examined. In the tonic red muscles, varicose nerve endings immunoreactive for both calcitonin gene-related peptide and substance P were found spread over the surface of the muscle fibers, but in the twitch white muscles only scattered nerve endings immunoreactive for calcitonin gene-related peptide were found. At the electron microscopic observation, dense electron products immunoreactive for calcitonin gene-related peptide and for substance P (SP) were detected in the motor nerve endings making synapses on the muscle fibers of the red muscles. In the spinal cord, all of the motor neurons showed immunoreactivity to calcitonin gene-related peptide, but the motor neurons immunoreactive for substance P were restricted to the ventrolateral group that has been shown to project predominantly to the red muscles. These results suggest that the motor neurons innervating the red and white muscles of the goldfish are distinct in their neuropeptide content. The present study also raises the possibility that SP might be related to the unique physiological properties of the tonic type red muscles, probably by direct binding to the acetylcholine receptors. (C) 2000 Elsevier Science Inc.

DOI： 10.1016/S0361-9230(00)00295-1

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Immunoreactivity for galanin was examined in the sympathetic preganglionic neurons in the spinal cord, adrenal glands, sympathetic ganglia, and some sensory ganglia of the filefish Stephanolepis cirrhifer. Galanin-immunoreactive neurons were found only in the rostral parr, but not in the caudal part of the central autonomic nucleus (a column of sympathetic preganglionic neurons of teleosts). Many galanin-immunoreactive nerve terminals were found in contact with neurons in the celiac ganglia and the cranial sympathetic ganglia on bath sides of the body. Most neurons encircled by galanin-immunoreactive nerve fibers were negative for tyrosine hydroxylase. Galanin-immunoreactive nerve fibers were very sparse in the spinal sympathetic paravertebral ganglia. No galanin-immunoreactive nerve fibers were found in the adrenal glands. No sensory neurons of the trigeminal, vagal, or spinal dorsal root ganglia were positive for galanin-immunoreactivity. These results suggest that galanin-immunoreactive sympathetic preganglionic neurons have distinct segmental localization and might project specifically to a population of non-adrenergic sympathetic postganglionic neurons in the celiac and cranial sympathetic ganglia. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0165-1838(00)00073-4

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Serotonin-immunoreactive axonal components were observed in the central autonomic nucleus (CAN), a cell column of sympathetic preganglionic neurons in the rostral spinal card of the filefish Stephanolepis cirrhifer. Serotonin-positive axonal varicosities were seen around neuronal perikarya through the whole rostrocaudal extent of the CAN, although their distribution pattern in the rostral CAN was different from that in the caudal CAN. Electron microscopically, serotonin-positive axonal varicosities were found to make axodendritic and axosomatic synapses on CAN neurons. Many serotonin-positive neuronal cell bodies were seen in the raphe nuclei in the lower brainstem, whereas only a few were found in the spinal cord. Thus most of serotoninergic axons within the CAN were considered to originate from the raphe nuclei in the lower brainstem. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(00)00766-7

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

To examine the presence of nitric oxide synthase (NOS) in the sensory system of the glossopharyngeal and vagus nerves of teleosts, nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) activity and immunoreactivity for NOS were examined in the puffer fish Takifugu niphobles. The nitrergic sensory neurons were located in the ganglia of both the glossopharyngeal and the vagal nerves. In the vagal ganglion, positive neurons were found in the subpopulations for the branchial rami and the coelomic visceral ramus, but not for the posterior ramus or the lateral line ramus. In the medulla, nitrergic afferent terminals were found in the glossopharyngeal lobe, the vagal lobe, and the commissural nucleus. In the gill structure, the nitrergic nerve fibers were seen in the nerve bundles running along the efferent branchial artery of all three gill arches. These fibers appeared to terminate in the proximal portion of the efferent filament arteries of three gill arches. On the other hand, autonomic neurons innervating the gill arches were unstained. These results suggest that nitrergic sensory neurons in the glossopharyngeal and vagal ganglia project their peripheral processes through the branchial rami to a specific portion of the branchial arteries, and they might play a role in baroreception of this fish. A possible role for nitric oxide (NO) in baroreception is also discussed.

DOI： 10.1007/s004419900078

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

The infrared sensory membranes of the pit organs of pit vipers have an extremely rich capillary vasculature, which has been noted passim in the Literature, but never illustrated or studied in detail.
We rendered the pit vasculature visible in various ways, namely, by microinjection of India ink, by a combination of ink and succinate dehydrogenase staining, and by making resin casts for scanning electron microscope study. We also used transmission electron microscopy for identifying the types (arterioles, venules, capillaries) of blood vessels. Then we compared the pit vasculature with that of the retina and the dermis.
Good visualization of the vasculature was obtained with both ink and resin injection. Arterioles, venules, and capillaries could be distinguished with all methods used. The monolayer vasculature was denser in the pit membrane than in the retina or skin. Each loop of the network enclosed a small number of infrared receptors so that all receptors were in contact with a capillary on at least one side. The forward-looking areas of the pit had a denser network. than side-looking areas.
Since infrared rays cause nerve impulses by raising the temperature of individual receptors, the capillary network functions not only as a supplier of energy but also as a cooling mechanism to reduce afterimages. Thus the denser network in the forward-looking areas causes these areas to be more sensitive and have better image resolution than the rest of the membrane. Anat Rec 254:107-115, 1999. (C) 1999 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1097-0185(19990101)254:1<107::AID-AR14>3.0.CO;2-Y

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

The supramedullary cells (SMCs) are spinal neurons lying at the dorsal surface of teleosts. In the present study, we examined whether the SMCs of the puffer fish (Takifugu niphobles) might express gastrin/cholecystokinin-immunoreactivity as observed in some other teleosts. All the SMCs were immunoreactive for gastrin/cholecystokinin. On the other hand, many immunoreactive varicose nerve fibers were also found terminating in the mucous glands in the skin. In addition, immunoreactive fibers were sparsely distributed in the epidermal layer. No neuronal cells other than the SMCs showed gastrin/cholecystokinin-immunoreactivity centrally or peripherally. The results suggest that gastrin/cholecystokinin-immunoreactive axons in the cutaneous mucous glands and epidermal layer are axons of the SMCs. In View of the present findings, the possible nature of SMCs was discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(98)00869-6

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The sympathetic preganglionic neurons of the teleost, Halichoeres poecilopterus, were identified by retrograde axonal tracing. After horseradish peroxidase was applied to the sympathetic trunk, labeled neurons were found at the caudalmost level of the medulla, in the spinal cord near the fourth spinal nerve root (rostral spinal group), and in the spinal cord from rostral to the sixth spinal nerve root to caudal to the tenth spinal nerve root (caudal spinal group). The rostral spinal group has three cell columns segregated mediolaterally from the central gray zone to the lateral funiculus. Labeled neurons were found predominantly on the side ipsilateral to the application. In the caudal spinal group, labeled neurons were found bilaterally in the central gray zone. This condition is different from that previously reported in the puffer fish and filefish. The labeling in the medulla suggests that the preganglionic neurons in the brainstem may send fibers to the sympathetic trunk of this fish, although their peripheral targets are unknown.

DOI： 10.1016/S0165-1838(97)00099-4

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the cranial sensory ganglia and brainstem of the banded dogfish, Triakis scyllia. Positive neurons were found in the vagal sensory ganglion projecting to the coelomic organs, but not in those projecting to the gills or the lateral line organs. Nerve terminals in the vagal lobe were also positive. No positive neurons were found in the glossopharyngeal, facial, or trigeminal sensory gang(ia. These results suggest that use of nitric oxide in the vagal sensory transmission from the coelomic organs may have been maintained in the evolutionary process from fish to mammals. (C) 1997 Elsevier Science Ireland Ltd.

DOI： 10.1016/S0304-3940(97)00835-5

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Previous studies have shown that the sympathetic preganglionic neurons of teleosts send axons to the sympathetic trunk on the contralateral side. After severing the spinal nerve roots at a level proximal to the sympathetic ganglia (i.e., nerve roots containing the preganglionic axons) on one side of puffer fish, Takifugu niphobles, horseradish peroxidase was applied to the other side of the sympathetic trunk. Retrogradely labeled sympathetic preganglionic neurons were found bilaterally in the central autonomic nucleus (a distinct cell column in the rostral part of the spinal cord). The contralaterally labeled neurons were located almost exclusively in the caudal part of the nucleus. These results suggest that some sympathetic preganglionic neurons in teleosts, unlike those in other vertebrates, send their axons across the midline to the contralateral nerve roots. (C) 1997 Elsevier Science B.V.

DOI： 10.1016/S0165-1838(97)00072-6

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

The sympathetic trunk of teleosts extends into the cranial levels, forming the cranial sympathetic ganglia. When horseradish peroxidase was applied to the trigeminal sympathetic ganglion (a sympathetic ganglion at the level of the trigeminal nerve) of the puffer fish, Takifugu niphobles, retrogradely labeled neurons were found in the central autonomic nucleus (a distinct cell column in the rostral part of the spinal cord). The central autonomic nucleus has been known to contain preganglionic neurons projecting to the sympathetic ganglia at the spinal levels. Thus, the present results indicate that the central autonomic nucleus in the spinal cord of teleosts contains not only preganglionic neurons projecting to the sympathetic ganglia at the spinal levels, but also neurons projecting to the sympathetic ganglia at the cranial levels.

DOI： 10.1016/0304-3940(96)12840-8

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

Little is known about the spinal sympathetic organization in teleosts. We examined the location of the sympathetic preganglionic neurons with horseradish peroxidase (HRP) labeling. After HRP application to the sympathetic trunk or celiac ganglion, labeled neurons were found just dorsal - dorsolateral to the central canal. They form a cell column (central autonomic nucleus) at the level of the posterior rootlet of the first spinal nerve to the third spinal nerve. HRP application to the sympathetic trunk produced labeling in almost the entire central autonomic nucleus, but HRP application to the celiac ganglion produced labeling in only the rostral half of the central autonomic nucleus. These results suggest that there is some topographical arrangement in the rostrocaudal part of the central autonomic nucleus. On the other hand, the fact that the sympathetic preganglionic neurons are within a single cell column and have no mediolateral segregation means that the target-related or function-associated mediolateral arrangement found in tetrapods is lacking in this species. We also found some labeling in the central autonomic nucleus after HRP application to the cranial nerves. This may indicate that the preganglionic neurons project to the cranial nerves.

DOI： 10.1007/s004410050571

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

The supramedullary cells (SMCs) of teleosts have been studied for nearly 100 years, but their peripheral connections have remained obscure. We examined the supramedullary cells of the puffer fish, Takifugu, niphobles, using horseradish peroxidase transport. Horseradish peroxidase labeling was found bilaterally after application to the trigeminal, the posterior branch of the vagal, and the spinal nerves. No labeled neurons were found after application to the anterior or visceral branches of the vagal nerve. Thus, labeled SMCs were found only after application to the nerves containing cutaneous branches.
Some rostrocaudal topographical labeling was found after selective application to each of the four branches of the trigeminal nerve. Labeled neurons were more common in the rostral than in the central or caudal part of the SMC region. Some topographical labeling was also found after application to the first, second, and third spinal nerves, but the topography was not very clear, and there was considerable overlap in the distribution of labeled cells. The sum total of labeled SMCs after unilateral horseradish peroxidase application to each peripheral nerve was more than three times the total number of ipsilateral SMCs, indicating that a single SMC projects several peripheral processes into different nerves.
From these results, and taking previous studies into consideration, we propose that supramedullary neurons have a phylogenetic relationship with the spinal dorsal cells of the lamprey and with the extramedullary cells of the amphibian embryo. (C) Wiley-Liss, Inc.

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI PUBL IRELAND LTD  

Enzyme histochemistry combined with horseradish peroxidase retrograde tracing demonstrated NADPH-diaphorase activity in the spinal sympathetic preganglionic neurons in the spinal cord of the filefish, Stephanolepis cirrhifer; these neurons with NADPH-diaphorase activity were located just dorsal and lateral to the central canal. The results indicate that nitric oxide is synthesized in the spinal sympathetic preganglionic neurons of filefish.

DOI： 10.1016/0304-3940(95)11587-M

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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DOI： 10.1182/blood-2018-171

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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担当区分：筆頭著者,　責任著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2011.07.920

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.ijdevneu.2006.09.076

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：HISTOCHEMICAL SOC INC  

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記述言語：日本語   出版者・発行元：(一社)日本解剖学会  

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