| Co-Investigator(Kenkyū-buntansha) |
OSAKA Toshimasa Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (30152101)
WATANABE Kikuko Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (90211672)
URADE Yoshihiro Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice-Hea, 第2研究部, 研究副部長 (10201360)
MATSUMURA Hitoshi Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice-Hea, 第2研究部, 研究副部長 (50173886)
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| Research Abstract |
Our research group found the sleep-promoting effect of prostaglandin (PG) D_2 and the awaking effect of PGE_2. The mechanisms underlying these effects have been studied in the present research project. We showed by use of in situ hybridization and immunocytochemical techniques that the brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, is abundantly expressed in the leptomeninges covering the surface of the brain, as well as choroid plexus, where cerebrospinal fluid (CSF) is produced. Interestingly, the beta-trace protein, the second most abundant protein in the human CSF,was identified as the brain PGD synthase, in the collaborative studies with foreign research groups. The site of action for the sleep-promoting effect of PGD_2 had been postulated to be located in the preoptic area, a sleep center ; however, our recent experimental results clearly 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. We also demonstrated that the concentration of PGD_2 in the 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 underlying 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 inferred to be 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.
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