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

ドーパミンＤ２受容体による覚醒調節分子機構

多巴胺D2受体调节觉醒的分子机制

基本信息

批准号：
25515007
负责人：
黄志力
金额：
$ 3.24万
依托单位：
公益財団法人大阪バイオサイエンス研究所
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2013
资助国家：
日本
起止时间：
2013-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25515007/
关键词：
caudate-putamen dopamine D2 receptor locomotor activity nucleus accumbens sleep wakefulness

项目摘要

During the last year, we clarified neuroanatomical location of dopamine D2 receptor (D2R) in maintaining wakefulness.We designed short-hairpin RNA of D2R carried by adeno-associated virus (AAV) to knockdown D2R in caudate-putamen (CPU), core of nucleus accumbens (NAc core) and shell of NAc (shell). The locomotor activity bioassay was performed using the infra sensors. EEG recordings were performed and automatically scored off-line by 10-s epochs as wakefulness, non-rapid eye movement (non-REM, NREM), and REM sleep by SleepSign. In addition, we also designed the AAV carrying human D2R gene (AAV-hD2R) to focally rescue the D2R in D2R KO mice.After knockdown of D2R in the NAc core, the mice showed decreased locomotor activity during both day and night periods under the basal conditions, compared to the control mice. For the sleep-wake profile, core D2R knockdown mice exhibited a significant decrease in wakefulness, with a concomitant increase in NREM and REM sleep. While the D2R were rescued, mice showed an increase in locomotor activity. In mice with knockdown of D2R in NAc shell in WT or rescue of D2R in the KO mice, there were no significant changes in locomotion and sleep-wake profiles.After knockdown of D2R in the CPU, the mice exhibited decreased locomotor activity, whereas there were no significant changes in sleep-wake profiles.In conclusion, D2R in the NAc core plays an essential role in the maintenance of wakefulness. However, D2R in the CPU is important in controlling movement whereas D2R in NAc shell does not mediate the arousal and locomotion.

在过去的一年里，我们阐明了多巴胺D2受体(D2R)在维持觉醒中的神经解剖学定位。我们设计腺相关病毒(AAV)携带的D2R的短发夹状RNA，在尾壳核(CPU)、伏核核心(NAC Core)和NAC壳(Shell)中击倒D2R。使用红外线传感器进行运动活性生物测定。进行脑电记录，并通过SleepSign对10-S时代的清醒、非快速眼动(非快速眼动，非快速眼动)和快速眼动睡眠进行自动脱机评分。此外，我们还设计了携带人D2R基因的AAV(AAV-hD2R)来集中拯救D2R KO小鼠中的D2R。在NAC核心区域敲除D2R后，小鼠在基础条件下的白天和夜间的运动活动都比对照组小鼠减少。对于睡眠-觉醒曲线，核心D2R基因敲除小鼠的觉醒程度显著降低，伴随而来的是NREM和REM睡眠的增加。当D2R获救时，小鼠的运动活动增加。在WT中NAC壳D2R被敲除的小鼠和KO小鼠中，D2R被敲除的小鼠的运动和睡眠-觉醒轮廓没有明显变化。在CPU中D2R被敲除后，小鼠的运动活动减少，而睡眠-唤醒轮廓没有明显变化。然而，CPU中的D2R在控制运动中起重要作用，而NAC壳中的D2R不参与觉醒和运动的调节。