| Co-Investigator(Kenkyū-buntansha) |
TANAKA Fukuko Yokohama City University, Graduate School of Medicine, Physiology, Visiting Professor (40046066)
TOSHIYA Funabashi Yokohama City University, Graduate School of Medicine, Physiology, Associate Professor (70229102)
TAKASE Kenkichi Yokohama City University, Graduate School of Medicine, Physiology, Assistant Professor (80381474)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Septo-hippocampal cholinergic neurons play a significant role in the spatial learning and memory function. We recently revealed a marked sex difference in the profile of 24-h acetylcholine (Ach) release in the hippocampus. In experiment I, to examine the role of sex hormones in the 24-h ACh release in the hippocampus, in vivo microdialysis study was performed in intact, gonadectomized (Gdx), gonadectomized testosterone-primed (Gdx+T), and gonadectomized estadiol-17β-primed (Gdx+E) rats, under the freely moving condition for more than 24 hours. The dialysate was collected from the dorsal hippocampus at 20-min intervals, and spontaneous locomotor activity was simultaneously monitored in the same subject. Although the sex-specific ACh release profile was observed in intact male and cycling female rats, the ACh release during the dark phase was severely attenuated in both sexes of Gdx rats. Both Gdx+T male rats and Gdx+E female rats successfully restored the ACh release during the dark pha
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se, while neither Gdx+T female rats nor Gdx+E male rats restored each profile. Although Gdx significantly decreased in the correlation coefficient between the ACh release and the spontaneous locomotor activity, both Gdx+T male rats and Gdx+E female rats successfully restored the correlation coefficient. In experiment II, to further examine the short-term effect of sex hormones on the ACh release in the hippocampus, testosterone (2 mg) or estadiol-17β (40 μg) was subcutaneously injected in Gdx male and Gdx female rats, respectively. Testosterone injection in Gdx male rats gradually, but significantly increased the ACh release within the first few hours, and it restored the ACh release up to the level in intact male rats within 10 hours. Similarly, estradiol-17β injection in Gdx female rats also increased the ACh release within the first few hours, and restored the ACh release up to the level in cycling female rats within 10 hours. Oil injection showed no significant effects on the ACh release. Present results demonstrated that (1) testosterone in male rats as well as estadiol-17β in female rats are essential to maintain the normal profile of ACh release in the hippocampus, (2) sex hormones may have a short-term effect on the ACh release. Less
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