Estrogenic Effect on Hippocampal Theta Rhythm and Memory

雌激素对海马 Theta 节律和记忆的影响

• 批准号: 6639148
• 负责人: CSABA LERANTH
• 金额: $ 30.23万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-06 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639148
• 关键词: atropine; behavioral /social science research tag; cell population study; chordate locomotion; dendrites; electron microscopy; electrophysiology; estrogen receptors; estrogens; estrus; exploratory behavior; glutamate receptor; hippocampus; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; memory; morphometry; neuroanatomy; neurons; neurophysiology; neuropsychology; northern blottings; ovariectomy; receptor expression

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 卵巢切除大鼠中的雌激素治疗可增强记忆的性能 任务。同样，人类的观察表明雌激素的有益作用 对阿尔茨海默氏病认知功能的治疗。但是，那些细胞 直接参与记忆过程的性腺激素的目标是 病了。唯一的固体观察是全身激素 操纵导致刺的密度变化和变化 NMDA受体的免疫染色强度 细胞。但是，海马主要神经元本身并不小，只有一个小 中间神经元的种群包含核雌激素受体。另一方面 手，皮层下区域的神经元，包括内侧隔膜带 Broca（MSDB），上区域（SUM）和中间Raphe（MR）包含 核雌激素受体，这些结构与 海马theta活性和长期增强的产生/调节。 此外，海马theta活动受到了极大的影响 改变循环雌激素的水平以及长期的结合 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外 通过影响这些皮层下区域来调节助记符过程 通过旨在检查MR，-MSDB和 - 卵巢切除大鼠中雌激素的体积： 1）海马锥体细胞的树突状脊柱密度变化； 2）离子型谷氨酸受体的mRNA和肽水平 海马； 3）海马theta活性。