| Project/Area Number |
21500313
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | 公益財団法人大阪バイオサイエンス研究所 (2011)
Osaka Bioscience Institute (2009-2010) |
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Principal Investigator |
HUANG Zhi-li 公益財団法人大阪バイオサイエンス研究所, 分子行動生物学部門, 研究副部長 (10321704)
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| Co-Investigator(Kenkyū-buntansha) |
URADE Yoshihiro 大阪バイオサイエンス研究所, 分子行動生物学部門, 研究部長 (10201360)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | アデノシン / 睡眠 / 遺伝子操作 / マウス / ラット / アデノ随伴ウィルス / アデノ随伴ウイルス |
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| Research Abstract |
Adenosine is a critical endogenous sleep-promoting substance involved in the regulation of sleep. Among the four subtypes of adenosine receptors, A_1 receptor(A_1R) and/or A_<2A> R subtypes have been reported to mediate the sleep-promoting effect of adenosine. Several lines of evidence suggest that adenosine acts via A_1R at the wake-promoting areas of cholinergic basal forebrain, histaminergic tuberomammillary nucleus, and/or orexinergic lateral hypothalamus to promote sleep. However, systemic or intracerebroventricular administration of an A_1R agonist has no clear effects on sleep promotion. Thus, wehypothesized that activation of A_1R in some brain regions may inhibit sleep. The ventrolateral preoptic nucleus(VLPO) has been considered to be a critical region for sleep induction. Our study found that activation of A_1R in the VLPO inhibited sleep and promoted wakefulness, while blockade of A_1R increased non-rapid movement(non-REM, NREM) and REM sleep and brief awakening(<16s), with the occurrence of sleep fragmentation, indicating that A_1R in the VLPO is involved in the maintenance of physiological wakefulness. When rats were subjected to sleep deprivation, activation of A_1R in rat VLPO reduced NREM and REM sleep during recovery period, increased the latency to NREM and REM sleep, and decreased delta power spectrum of NREM sleep. These results clearly indicate that A_1R in the VLPO is involved in the regulation of spontaneous sleep-wake cycle and sleep homeostasis. Immunohistochemistry staining and RT-PCR revealed that there is an expression of A_1R in the VLPO. These results clearly indicate that A_1R in the VLPO is involved in the regulation of spontaneous sleep-wake cycle and sleep homeostasis.
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