Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Neuropeptide Y (NPY) and its receptors affect blood pressure, feeding behavior, and neurogenesis. In this study, the distribution of neurons expressing NPY Y-5 receptor (Y-5) was examined in adult mouse central nervous system by immunohistochemistry. Y-5 protein localization was investigated using polyclonal anti-Y-5 antibody, which was successfully preabsorbed with Y-5 knockout brain tissues. The preabsorbed anti-Y-5 antibody did not react with Y-5 knockout brain tissues, thus meeting the "hard specificity criterion," which is the absence of staining in tissues genetically deficient for the antigen (Pradidarcheep et al., 2008). Y-5-positive neurons were found in most brain areas. Most Y-5 immunoreactivities were observed as dot-like structures adjacent to the plasma membrane, as expected for a cell membrane receptor. In situ hybridization showed that the Y-5 mRNA expression was correlated with the Y-5 protein level in each case and that it was probably controlled by the transcriptional regulation of the Y-5 gene. In the nuclei where Y-5 was expressed, Y-5 immunoreactivities were found mainly in the somatic and dendritic areas. The distribution patterns of the Y-5-positive cells that were broader than previously expected suggest important biological activities of the Y-5 in many brain areas.

DOI： 10.1016/j.brainres.2016.10.026

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Pharmacological Society  

DOI： 10.1254/fpj.137.166

PubMed

CiNii Article

CiNii Books

researchmap

Other Link： https://jlc.jst.go.jp/DN/JALC/00367068590?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)   Publisher：W J G PRESS  

Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexigenic neuropeptides such as alpha-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene expressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mechanism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior. (C) 2008 The WJG Press. All rights reserved.

DOI： 10.3748/wjg.14.6312

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本薬理学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

researchmap

Language：Japanese   Publisher：新潟医学会  

中枢での摂食制御は視床下部に存在する摂食関連神経ペプチドが重要な働きをしている. その中でニューロペプチドY (NPY) は最も強い摂食誘導作用を示す. マウスに絶食負荷を行うと視床下部弓状核 (ARC) でのNPY発現が増加し, これによって摂食行動が促進される. 別の摂食関連神経ペプチドであるガラニンは, NPYと同様に摂食を誘導する作用を持ち, 脳内へ投与すると摂食行動が促進される. しかし, ガラニンが脳内でどのようなメカニズムで摂食行動を調節しているかは不明である. 今回の研究では, 野生型マウス (C57BL/6N) に50時間絶食負荷を施し, 視床下部のどの神経核でガラニン遺伝子発現が変化しているか検討するために in situ ハイブリダイゼーションを行った. その結果, 絶食負荷によって視床下部背内側核 (DMN) でのガラニンmRNA発現が増加した. この神経核には, ARCから摂食誘導性のNPY神経が投射しており, NPY受容体 (Y1受容体, Y5受容体) が発現している. そのため, 絶食負荷によるガラニンmRNA増加がY1受容体及びY5受容体を介して引き起こされるという仮説を立て, Y1受容体又はY5受容体をノックアウトしたマウスに絶食負荷を行い, 絶食によるDMNでのガラニンmRNA発現を in situ ハイブリダイゼーション法により検討した. その結果, Y1受容体又はY5受容体をノックアウトしたマウスでは, DMNでのガラニン発現増加が消失した. さらに, DMNでのY1受容体及びY5受容体をsiRNA発現ベクターによりノックダウンすることでも, 絶食負荷によるガラニン発現増加が消失した. さらに, 通常では絶食後の再摂食行動が促進されるが, DMNでのY1受容体及びY5受容体をノックダウンすることで, 絶食後の再摂食行動増加が抑制された. これらの結果より, DMNに発現するガラニン神経は, NPYによるY1受容体及びY5受容体を介して活性化され, 絶食後の摂食行動増加に関与していると考えられた.

CiNii Article

CiNii Books

researchmap