MOLECULAR STUDY OF ESTROGEN INDUCED SYNAPTOGENESIS

长期目标是了解雌激素在学习和学习中的作用 记忆，在海马神经元功能，在突触发生，和 这些细胞的故障与人类疾病有何关联。临床 研究表明，雌激素治疗会影响女性~S空间任务， 言语记忆和精细的运动技能，并改善精神状态 女性阿尔茨海默病患者中~S。在大鼠体内的平行研究 已证明雌激素对认知功能有影响。此外， 在细胞水平上，已经证明雌激素诱导树突状细胞。 海马神经元中的棘突和新突触。因此，它是 迫切需要了解雌激素的分子机制 诱导海马神经元突触发生，因为：a) 突触发生是最基本的神经元活动之一， 学习和记忆的关键细胞基础；和b)海马体 是一个重要的大脑区域，它解释了许多学习和 内存任务。这项拟议研究的具体目的是确定 这一过程的分子组成和机制。一个 已建立了海马区细胞培养系统，其中 雌激素治疗可以诱导突触发生。利用这一点 系统，a)已知在突触发生中重要的分子，如 作为cAMP反应元件结合蛋白(CREB)蛋白 将检测磷酸酶I(PPI)和NMDA受体 转录、翻译和磷酸化的变化，与或 在没有雌激素诱导的情况下；b)该途径的假说将是 测试；c)将使用mRNA差异显示技术来识别 雌激素诱导中诱导或抑制的新分子 突触发生。

The long term goal is to understand estrogen's role in learning and memory, in hippocampal neuron function, in synaptogenesis, and how the malfunction of these is relevant to human diseases. Clinical study reveals that estrogen treatment affects women~s spatial tasks, verbal memory, and fine motor skills, and improves the mental status of female Alzheimer~s patients. Parallel study in rat also demonstrated estrogens impact on cognitive functions. Furthermore, at the cellular level, it has been shown that estrogen induces dendritic spines and new synapses in the hippocampal neurons. Hence, it is imperative to understand the molecular mechanisms of the estrogen induced synaptogenesis in hippocampal neurons, because: a) synaptogenesis is one of the most fundamental neuronal activities and a critical cellular basis for learning and memory; and b) hippocampus is an essential brain region that accounts for many learning and memory tasks. The specific aim of this proposed study is to identify molecular components and mechanisms of this process. A hippocampal cell culture system has been developed, in which synaptogenesis can be induced by estrogen treatment. Utilizing this system, a)molecules known to be important in synaptogenesis, such as cAMP responsive element binding protein (CREB), protein phosphotase I (PPI) and NMDA receptor will be examined for their changes in transcription, translation and phosphorylation, with or without estrogen induction; b) a hypothesis of the pathway will be tested; c)mRNA differential display technique will be used to identify new molecules that are induced or suppressed in estrogen induced synaptogenesis.