MOLECULAR STUDY OF ESTROGEN INDUCED SYNAPTOGENESIS

长期的目标是了解雌激素在学习中的作用， 记忆，海马神经元功能，突触发生， 它们的功能失常与人类疾病的关系。 临床 研究表明，雌激素治疗影响女性的空间任务， 语言记忆和精细运动技能，并改善精神状态 老年痴呆症女性患者 在大鼠中进行的平行研究也 雌激素对认知功能的影响。 此外，委员会认为， 在细胞水平，已经表明雌激素诱导树突状细胞 海马神经元中的棘和新突触。 因此， 必须了解雌激素的分子机制 诱导海马神经元的突触发生，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 是一个重要的大脑区域，负责许多学习， 记忆任务 这项研究的具体目的是确定 这一过程的分子组成和机制。 一 海马细胞培养系统已被开发，其中， 雌激素治疗可以诱导突触发生。 利用该 系统，a）已知在突触发生中重要的分子，例如 作为cAMP反应元件结合蛋白（CREB），蛋白质 将检查磷酸酶I（PPI）和NMDA受体的 转录、翻译和磷酸化的变化，或 没有雌激素诱导; B）该途径的假设将是 c）mRNA差异显示技术将用于鉴定 在雌激素诱导下被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.