权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Sleep and Gut Functions : Electrophysiological Actions of Sleep-Related Peptides in the Enteric Nervous System

睡眠和肠道功能：肠神经系统中睡眠相关肽的电生理作用

基本信息

批准号：
17605004
负责人：
KATAYAMA Yoshifumi
金额：
$ 1.6万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17605004/
关键词：
Sleep-Wake Gut Functions Enteric Nervous System Orexins Ghrelin Motilin Neuropeptide Y Electrophysiology 睡眠脳

项目摘要

Many neuropeptides are established or proposed as neurotransmitter or neuromodulators not only in the brain but also in the gut, and termed brain-gut peptides. Since some of these peptides are known to be involved in controlling feeding and sleep, they might provide some possible clues from feeding via gut functions to sleep. In the present project, we investigated their electrophysiological actions on enteric neurons as well as their actions on sleep and feeding behaviors.Intracellular recordings were made in vitro from myenteric neurons of the ileum and submucosal neurons of the cecum of guinea-pigs to examine actions of the sleep-related peptides on neuronal electrical properties and ganglionic transmission. Both of orexin A and B caused membrane depolarizations in a group of myenteric neurons and facilitated fast EPSPs mediated by either ACh or ATP. Motilin depolarized a small population of myenteric neurons and inhibited fast EPSPs. Ghrelin, known to have structural and function-r … More elated similarities to motilin, exerted multiple actions, either membrane depolarization or hyperpolarization, and depressed fast EPSPs. Neuropeptide Y and neuropeptide Y-related peptides depolarized myenteric neurons and inhibited fast EPSPs. PACAP also caused neuronal depolarization and inhibited fast EPSP in the submucosal plexus. Since the peptides examined here did not change the neuronal sensitivity to ACh and ATP, orexins facilitated, whereas others inhibited, synaptic transmission, by increasing or decreasing the amount of released transmitters. The brain-gut "sleep-related" peptides, examined here, modulated neuronal activity and synaptic transmission in the enteric nervous system of guinea-pigs. It is concluded that these are involved in controlling gut functions" possibly leading to affecting feeding behavior.Primary sensory dorsal root ganglion neurons in culture, isolated from neonatal rats, responded to orexin by inducing inward currents of about 100 pA when voltage clamped at -60 mV.Third ventricle intracerebroventricular infusion of orexins and their related compounds demonstrated that orexins regulated the rat sleep-wake cycle by increasing REM and non-REM sleep via orexin receptor type 2. Intraperitoneal application of neuropeptide Y agonist enhanced non-REM sleep and feeding behavior of rats. The actions of ghrelin and motilin infused into third cerebroventricule are now under observations and to be continued.It is premature to describe general relationship between sleep and gut function on the basis of the present results obtained from the limited regions, the ileum and cecum of one animal species, guinea-pig, because the digestive tract is different from animal to animal, reflecting their feeding behavior. Less

许多神经肽被确立或提议作为神经递质或神经调节剂，不仅在大脑中而且在肠道中，并被称为脑肠肽。由于已知其中一些肽参与控制进食和睡眠，因此它们可能提供一些从通过肠道功能进食到睡眠的可能线索。在本项目中，我们研究了它们对肠神经元的电生理作用以及它们对睡眠和进食行为的作用。在体外对豚鼠回肠肌间神经元和盲肠粘膜下神经元进行细胞内记录，以检查睡眠相关肽对神经元电特性和神经节传递的作用。食欲素 A 和 B 都会引起一组肌间神经元的膜去极化，并促进由 ACh 或 ATP 介导的快速 EPSP。胃动素使一小部分肌间神经元去极化并抑制快速 EPSP。已知胃饥饿素在结构和功能上与胃动素有相似之处，可以发挥多种作用，可以使膜去极化或超极化，并抑制快速 EPSP。神经肽 Y 和神经肽 Y 相关肽使肌间神经元去极化并抑制快速 EPSP。 PACAP 还引起神经元去极化并抑制粘膜下丛中的快速 EPSP。由于此处检查的肽不会改变神经元对 ACh 和 ATP 的敏感性，因此食欲素通过增加或减少释放的递质的量来促进突触传递，而其他肽则抑制突触传递。这里检查的脑肠“睡眠相关”肽调节豚鼠肠神经系统中的神经元活动和突触传递。结论是这些参与控制肠道功能，可能导致影响进食行为。从新生大鼠中分离出来的培养物中的初级感觉背根神经节神经元，当电压钳制在-60 mV时，通过诱导约100 pA的内向电流对食欲素做出反应。第三脑室脑室内输注食欲素及其相关化合物表明，食欲素通过 2 型食欲素受体增加 REM 和非 REM 睡眠来调节大鼠睡眠-觉醒周期。腹膜内应用神经肽 Y 激动剂可增强大鼠的非 REM 睡眠和进食行为。注入第三脑室的生长素释放肽和胃动素的作用目前正在观察中，并将继续进行。根据从有限区域获得的现有结果来描述睡眠和肠道功能之间的一般关系还为时过早。一种动物豚鼠的回肠和盲肠，因为不同动物的消化道不同，反映了它们的摄食行为。少