Role of gonadal steroids on the in vivo acetylcholine release in the hippocampus

性腺类固醇对海马体内乙酰胆碱释放的作用

基本信息

批准号：
18590219
负责人：
MITSUSHIMA Dai
金额：
$ 2.5万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590219/
关键词：
aPKC PAR-1 epithelial cells polarity basal laminina dvstroglycan cancer muscular dystrophy 海馬行動リズム

项目摘要

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 … More 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

隔海马胆碱能神经元在空间学习和记忆功能中发挥着重要作用，我们最近在实验 I 中发现海马 24 小时乙酰胆碱 (Ach) 释放情况存在显着的性别差异，以检验性别的作用。海马 24 小时 ACh 释放中的激素，在完整、性腺切除 (Gdx)、性腺切除的体内进行了体内微透析研究睾酮引发（Gdx+T）和去腺激素17β引发（Gdx+E）大鼠，在自由活动条件下超过24小时，每隔20分钟从背侧海马收集透析液，并自发收集。同时监测同一受试者的运动活动，尽管在完整的雄性和循环雌性大鼠中观察到性别特异性的乙酰胆碱释放曲线，但在黑暗阶段观察到乙酰胆碱释放。 Gdx+T 雄性大鼠和 Gdx+E 雌性大鼠在黑暗阶段均成功恢复了 ACh 释放，而 Gdx+T 雌性大鼠和 Gdx+E 雄性大鼠均未恢复。尽管Gdx显着降低了ACh释放与自发运动活动之间的相关系数，但Gdx+T雄性大鼠和Gdx+E雌性大鼠均成功地恢复了相关系数。为了进一步研究性激素对海马乙酰胆碱释放的短期影响，分别在Gdx雄性大鼠和Gdx雌性大鼠中皮下注射睾酮（2mg）或雌二醇-17β（40μg）。大鼠的ACh释放逐渐增加，但在最初的几个小时内显着增加，并在10小时内将ACh释放恢复到完整雄性大鼠的水平。 Gdx 雌性大鼠中注射雌二醇-17β 也会在最初的几个小时内增加 ACh 释放，并在 10 小时内将 ACh 释放恢复到循环雌性大鼠的水平。目前的结果表明，油注射对 ACh 释放没有显着影响。 (1) 雄性大鼠中的睾酮和雌性大鼠中的 estadiol-17β 对于维持海马中 ACh 释放的正常分布至关重要，(2) 性激素可能对乙酰胆碱释放较少。