Androgen Receptors and Hippocampal Function

雄激素受体和海马功能

• 批准号: 9604723
• 负责人: Robert Handa
• 金额: $ 28.48万
• 依托单位: Loyola University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9604723&HistoricalAwards=false
• 关键词: Androgen; Receptors; Hippocampal; Function

9604723 Handa The hippocampus is a forebrain structure of the temporal lobe, constituting an important part of the limbic system and of the Papez's circuit. Its general anatomy and connections to other regions of the brain are well defined. Functions that depend upon the hippocampus are recognition of novelty, learning and memory. Indeed it is believed that this brain region serves as a spatial map that helps us remember where we have been. Recently, it has been shown that the hippocampus contains a high concentration of androgen receptors suggesting that testosterone may influence this region of the brain. Moreover, sex differences in cognitive functions have been reported. Despite recent data demonstrating that the hippocampus is a major target for androgen and there are male-female differences in spatial memory and in learning, few studies have examined the neural mechanisms by which androgen can alter hippocampal function or hippocampal cell parameters. Recently, Dr. Handa showed that androgens influence hippocampal function by altering the n-methyl-d-aspartate (NMDA) receptors, which are important for glutamate neurotransmission and the underlying sensitivity to neurotoxic insults such as anoxia and chronic stress. He will now combine his expertise in molecular and cellular neuroendocrinology with Dr. Beck's talents in neurophysiology to carry out an integrative series of studies to examine the effects of androgen on hippocampal synaptic plasticity. They will examine the effects of androgen on hippocampal cell morphology, NMDA receptor composition and function, and enzyme activity. The results from these studies will provide new knowledge on the role that steroid hormones play in modulating a brain region that occupies a central role in regulating multiple non- reproductive behaviors.

9604723 Handa 海马体是颞叶的前脑结构，构成边缘系统和帕佩斯环路的重要组成部分。 它的一般解剖结构以及与大脑其他区域的连接都有明确的定义。 依赖于海马体的功能是对新奇事物的识别、学习和记忆。 事实上，人们相信这个大脑区域充当空间地图，帮助我们记住我们去过的地方。 最近，研究表明海马体含有高浓度的雄激素受体，这表明睾酮可能会影响大脑的这个区域。 此外，据报道，认知功能存在性别差异。 尽管最近的数据表明海马体是雄激素的主要目标，并且男女在空间记忆和学习方面存在差异，但很少有研究探讨雄激素改变海马功能或海马细胞参数的神经机制。 最近，Handa 博士表明，雄激素通过改变 NMDA 受体来影响海马功能，NMDA 受体对于谷氨酸神经传递以及对缺氧和慢性压力等神经毒性损伤的潜在敏感性非常重要。 他现在将把他在分子和细胞神经内分泌学方面的专业知识与贝克博士在神经生理学方面的才能结合起来，开展一系列综合研究，以检查雄激素对海马突触可塑性的影响。他们将检查雄激素对海马细胞形态、NMDA 受体组成和功能以及酶活性的影响。 这些研究的结果将提供关于类固醇激素在调节大脑区域中的作用的新知识，该区域在调节多种非生殖行为中发挥着核心作用。