ESTROGEN, GLUTAMATE RECEPTOR IN PLASTICITY AND ALZHEIMER'S DISEASE

这个项目解决了DUAL背后的细胞机制 雌激素在阿尔茨海默病患者中的作用，即 改善认知功能障碍，降低心力衰竭发生率 接受雌激素替代疗法的女性的AD。这些影响 雌激素暗示雌激素或某些马的雌激素成分 作为认知增强剂和/或神经保护剂。 这些假说将在突触的体外模型中得到验证 可塑性和神经退行性变。长时程增强(LTP)是 被广泛认为代表了一种信息的细胞机制 储存和调节LTP的化合物已被发现 调节学习和记忆过程。LTP诱导和 表达严重依赖于两类变力作用 受体分别为NMDA和AMPA受体。 因此，具体目标1和2将旨在确定 急、慢性雌激素对大鼠海马区雌激素的影响 在培养中保存几个星期的切片；特性 对AMPA和NMDA受体和LTP的性质的影响。 用兴奋性毒素或β-内毒素处理培养的海马片 淀粉样多肽(β-AP)引起选择性神经元损伤 它表现出AD发生的神经元死亡的几个特征。 因此，特定的AIMS 3和4将评估神经保护 雌激素在这些模型中的作用。雌激素在这些组织中的作用 体外系统将与其在体外培养中的效果进行比较。 分离的神经元以及在体内的突触模型 可塑性和神经退行性变。

This project addresses the cellular mechanisms underlying the dual actions of estrogen in women with Alzheimer's Disease, i.e., the improvement of the cognitive deficits and the reduced incidence of AD in women with estrogen replacement therapy. These effects of estrogen suggest that estrogen or some equine estrogen constituent acts as a cognitive enhancer and/oras a neuroprotective agent. These hypothesis will be tested in in vitro models of synaptic plasticity and neurodegeneration. Long-term potentiation (LTP) is widely considered to represent a cellular mechanism for information storage and compounds modulating LTP have been found to modulate learning and memory processes. LTP induction and expression are critically dependent on 2 classes of inotropic receptors, the NMDA and the AMPA receptors, respectively. Specific Aims 1 and 2 will therefore be directed at determining the effects of acute and chronic estrogen treatment of hippocampal slices maintained in culture for several; weeks on the characteristics of AMPA and NMDA receptors and on the properties of LTP. Treatment of cultured hippocampal slices with excitotoxin or beta- amyloid peptide (betaAP) produces selective neuronal damage which exhibits several features of neuronal death occurring in AD. Specific Aims 3 and 4 will therefore evaluate the neuroprotective effects of estrogen in these models. Effects of estrogen in these in vitro systems will be compared with its effects in cultures of dissociated neurons as well as in in vivo models of synaptic plasticity and neurodegeneration.