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

在这项研究中，我们通过多单元活动记录技术、脑内吸水聚合物注射和神经元细胞培养来研究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的kainate型受体，促进了跑步活动和交感神经系统，并且这些氨基酸从神经末梢的释放被GRBA突触前抑制。在超跑过程中，VMH可以发出指令供应能量基质，从而将运动和能量代谢同时结合起来。我们还发现下丘脑促性腺激素释放激素（GnRH）脉冲发生器的电活动被去甲肾上腺素促进，被阿片肽抑制。此外，GnRH脉冲发生器活性被肿瘤坏死因子抑制，肿瘤坏死因子是巨噬细胞通过前列腺素介导的机制释放的一种细胞因子。这表明，排卵前促性腺激素激增是由神经元机制诱导的，本质上不同于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，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。我们发现64-KDa蛋白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有关代谢和繁殖的问题。

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.