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Studies of neurophysiological regulation of sleep-wake states using animal models for sleep research

使用睡眠研究动物模型研究睡眠-觉醒状态的神经生理学调节

基本信息

批准号：
18603002
负责人：
HONDA Kazuki
金额：
$ 2.57万
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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18603002/
关键词：
Sleep disorder Non-REM sleep REM sleep Food intake Motilin Ghrelin Orexin Parkinson's Disease ドパミンナルコレプシーオレキシンドーパミン

项目摘要

In recent decades, many of the chemical and neuronal substrates involved in sleep-wake regulation have been identified. Recently, orexins A and B involved in the regulation of the feeding and arousal states, were identified. An intracerebroventricular (icv) infusion of both orexins A and B has been observed to induce arousal effects in rats. In the present studies, we investigated the involvement of humoral factors in neurophysiological regulation of sleep-wake states and animal models for sleep research.1. An icv infusion of orexin A for a 5-h period markedly increased the amount of wakefulness over the baseline value. OX2R antagonist decreased orexin A-induced wakefulness. Although OX2R antagonist treatment alone slightly changed each sleep parameter, no significant difference was observed. Pretreatment with OX2R antagonist, significant inhibited orexin A-induced wakefulness in rats. The finding this study therefore suggest that OX2R involved in arousal state regulation.2. Motilin is known to regulate the feeding system. We investigated the effects of icv infusion of motilin (1, 10, 50, 100 nml) on the sleep-waking cycle in the freely behaving rats. Motilin at the dose of 100 nmol markedly increased the amount of wakefulness by 75.0% (p<0.05) over the baseline value. These finding suggest that motilin also modulates sleep-wake states and behavioral responses.3. Parkinson's Disease (PD) is a progressive neurodegenerative disease wherein dopaminergic neuron in the substantia nigra pars compacta (SNpc) are destroyed. In this study, α-synuclein transgenic (TG) mice for the diminished expression of dopaminergic neurons in SNpc were used to investigate sleep architecture, and compared to wild type (WT) mice. Analysis of sleep architecture had no significant differences between TG and WT mice. Further research on the influence of the dopaminergic system on the sleep-wake cycle using PD models is needed to validate the observed sleep-wake cycle disturbances.

近几十年来，许多参与睡眠-觉醒调节的化学物质和神经元底物已被确定。最近，食欲素A和B参与调节进食和唤醒状态，被确定。已经观察到脑室内（icv）输注食欲素A和B诱导大鼠的唤醒效应。本研究主要探讨体液因素对睡眠-觉醒状态的神经生理调节以及睡眠研究的动物模型. icv输注食欲素A 5小时，显著增加觉醒量超过基线值。OX 2 R拮抗剂减少食欲素A诱导的觉醒。虽然单独的OX 2 R拮抗剂治疗轻微改变了每个睡眠参数，但未观察到显著差异。OX 2 R拮抗剂预处理可显著抑制食欲素A诱导的大鼠觉醒。因此，本研究的发现提示OX 2 R参与了觉醒状态的调节.已知胃动素调节摄食系统。本实验观察了侧脑室注射胃动素（1，10，50，100 nml）对自由活动大鼠睡眠-觉醒周期的影响。100 nmol胃动素可使清醒次数增加75.0%（p<0.05）。提示胃动素对睡眠-觉醒状态和行为反应也有调节作用.帕金森病（Parkinson's Disease，PD）是一种进行性神经退行性疾病，其中黑质（substantia nigra pars rectata，SNpc）中的多巴胺能神经元被破坏。在这项研究中，α-突触核蛋白转基因（TG）小鼠的SNpc中多巴胺能神经元的表达减少，用于研究睡眠结构，并与野生型（WT）小鼠进行比较。睡眠结构分析在TG和WT小鼠之间没有显著差异。需要进一步研究多巴胺能系统对睡眠-觉醒周期的影响，使用PD模型来验证所观察到的睡眠-觉醒周期紊乱。