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：（改编自申请人的摘要）：最近的证据表明雌激素治疗卵巢切除大鼠可增强记忆力任务。同样，人类观察表明雌激素具有有益作用阿尔茨海默病认知功能的治疗。然而，那些蜂窝直接参与记忆过程的性腺激素的目标是定义不明确。唯一可靠的观察结果是全身荷尔蒙操作会导致脊柱密度的变化和结构的改变海马 CA1 锥体 NMDA 受体免疫染色强度细胞。然而，海马主要神经元本身没有，只有一小部分中间神经元群含有核雌激素受体。另一方面手，皮层下区域的神经元，包括内侧隔膜对角带 Broca (MSDB)、乳头上区 (SUM) 和中缝 (MR) 包含核雌激素受体，这些结构与海马θ活动和长期增强的产生/调节。此外，海马θ活动受循环雌激素水平的变化，与长期据信，增强作用与记忆过程有关。因此，假设雌激素除了直接影响海马体之外，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部 MR、-MSDB 和 -SUM 对卵巢切除大鼠施用雌激素： 1)海马CA1锥体细胞树突棘密度的变化； 2)离子型谷氨酸受体的mRNA和肽水平海马体； 3）海马θ活动。