| Co-Investigator(Kenkyū-buntansha) |
OSAKA Toshimasa Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (30152101)
SATOH Shinsuke Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (40270574)
WATANABE Kikuko Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (90211672)
URADE Yoshihiro Osaka Bioscience Institute Department of Molecular Behavioral Biology, Vice-Head, 第2研究部, 研究副部長 (10201360)
HAYAISHI Osamu Osaka Bioscience Institute, Director, 所長 (40025507)
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| Research Abstract |
The site of action for the sleep-promoting effect of prostaglandin (PG) D_2 had been postulated to be located in the preoptic area, a sleep center ; however, our experimental results showed that the real site of action is located in the ventral surface of a basal-forebrain region located rostral to the preoptic area. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle, as well as the diagonal band of Broca and the septal region. We also demonstrated that changes in the regional blood flow in this area are closely correlated with the changes in the sleep-wake state. The brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, was shown to be abundantly expressed in the leptomeninges covering the surface of the brain. The concentration of PGD_2 in the cerebrospinal fluid (CSF) of the rat was higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is postulated that PGD_2 synthesized in the membrane tissues surrounding the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signal produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2. The region including the ventral striatum may serve as an interface structure between, humoral and neuronal mechanisms for the sleep-wake regulation.
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