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CONTROL OF FEEDING AND SEX BEHAVIOR AND DISEASES BY MODULATING HYPOTHALAMIC FUNCTION

通过调节下丘脑功能控制进食和性行为及疾病

基本信息

批准号：
03304024
负责人：
TAKAHASHI Michio
金额：
$ 11.39万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

In this study, we examined neuronal machanisms in the hypothalamus controlling feeding behavior and reproductive function by means of multiunit activity recording technique, water-absorbent polymer injection into the brain, and neuronal cell culture. We found that endogenous excitatory amino acids acting on the Kainate-type receptor in the ventromedial nucleus of the hypothalamus (VMH) facilitated both running activity and the sympathetic nervous system, and that the release of such amino acids from the nerve terminal was presynaptically inhibited by GRBA. The VMH may issue commands to supply energy substrates during the hyper-running and thus integrate both exercise and energy metabolism at the same time. We also found that the electrical activity of the hypothalamic gonadotropin releasing hormone (GnRH) Pulse generator was facilitated by norepinephrine and inhibited by opioid peptides. Further, GnRH Pulse generator activity was found to be suppressed by tumor necrosis factor, a cytokine released from macrophages, via a prostaglandin mediated mechanism. It was suggested that preovulatory gonadotropin surge was induced by a neuronal mechanism that is intrinsically different from the GnRH pulse generator. We established a dissociated rat suprachiasmatic nucleus cell culture which provides a useful model for the analysis of a mammalian circadian system at the cellular level. We identified the 64-KDa protein which may be a part of the circadian clock mechanism. Through these studies, we will be able to resolve problems concerning metabolism and reproduction in the field of veterinary and medical sciences.

本研究采用多单位活动记录技术、脑内注射吸水性聚合物和神经细胞培养等方法，研究了下丘脑控制摄食行为和生殖功能的神经元机制。我们发现，内源性兴奋性氨基酸作用于下丘脑腹内侧核（VMH）中的红藻氨酸型受体，促进了跑步活动和交感神经系统，并且这种氨基酸从神经末梢的释放被GRBA突触前抑制。VMH可以在超跑期间发出命令来提供能量基质，从而同时整合运动和能量代谢。我们还发现去甲肾上腺素易化下丘脑促性腺激素释放激素（GnRH）脉冲发生器的电活动，而阿片肽则抑制它。此外，发现GnRH脉冲发生器活性通过前列腺素介导的机制被肿瘤坏死因子（一种从巨噬细胞释放的细胞因子）抑制。这表明，排卵前促性腺激素激增是由一种神经元机制，这是本质上不同的GnRH脉冲发生器。我们建立了一个分离的大鼠视交叉上核细胞培养，这为在细胞水平上分析哺乳动物的昼夜节律系统提供了一个有用的模型。我们鉴定了64-KDa蛋白，其可能是生物钟机制的一部分。通过这些研究，我们将能够解决兽医和医学领域的代谢和生殖问题。