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Estrogenic Effect on Hippocampal Theta Rhythm and Memory

雌激素对海马 Theta 节律和记忆的影响

基本信息

批准号：
6724951
负责人：
CSABA LERANTH
金额：
$ 30.23万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-06 至 2006-03-31
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from applicant's abstract): Recent evidence indicates that estrogen treatment in ovariectomized rats enhances performance on memory tasks. Similarly, human observations suggest a beneficial effect of estrogen treatment on cognitive function in Alzheimer's disease. However, those cellular targets of gonadal hormones that are directly involved in memory processes are ill defined. The only solid observations are that systemic hormonal manipulations result in changes in the density of spines and alterations in the intensity of immunostaining for NMDA receptor of hippocampal CAl pyramidal cells. However, hippocampal principal neurons themselves do not, only a small population of interneurons contains nuclear estrogen receptor. On the other hand, neurons in subcortical areas, including the medial septum diagonal band of Broca (MSDB), supramammillary area (SUM), and median raphe (MR) contain nuclear estrogen receptors, and these structures are associated with the generation/regulation of hippocampal theta activity and long term potentiation. Furthermore, hippocampal theta activity, which is greatly influenced by the changing levels of circulating estrogen, in conjunction with long-term potentiation is believed to be involved in memory processes. Therefore, the hypothesis that estrogen, in addition to influencing the hippocampus directly, regulates mnemonic processes by affecting these subcortical areas will be tested by experiments designed to examine the effects of intra-MR, -MSDB, and -SUM administration of estrogen in ovariectomized rats on: 1) changes in dendritic spine density of hippocampal CAl pyramidal cells; 2) mRNA and peptide levels of ionotropic glutamate receptors in the hippocampus; 3) hippocampal theta activity.

描述：（改编自申请人摘要）：最近的证据表明雌激素治疗卵巢切除大鼠增强记忆力的表现任务同样，对人体的观察表明，阿尔茨海默病认知功能的治疗。然而，这些细胞直接参与记忆过程的性腺激素的目标是不明确。唯一可靠的观察结果是，操作导致棘密度的变化和海马CA 1区锥体细胞NMDA受体免疫染色强度细胞然而，海马主神经元本身并不，只有一个小的，中间神经元群含有核雌激素受体。另另一方面，皮质下区域的神经元，包括内侧隔斜角带 Broca区（MSDB）、乳头体上区（SUM）和中缝（MR）包含核雌激素受体，这些结构与海马theta活性和长时程增强的产生/调节。此外，海马theta活动，这是很大的影响，循环雌激素水平的变化，增强作用被认为涉及记忆过程。因此假设雌激素，除了直接影响海马体，通过影响这些皮层下区域来调节记忆过程，通过旨在检查内MR，-MSDB，和 - 在卵巢切除大鼠中给予雌激素的总和： 1)海马CA 1区锥体细胞树突棘密度变化; 2)脑组织中离子型谷氨酸受体的mRNA和肽水平海马; 3)海马theta活动