成年海马齿回放射状胶质细胞样（RGLs）神经干细胞耗竭而导致的异常神经发生是阿尔茨海默病（AD）学习记忆功能受损的关键因素。我们前期研究发现LXRβ敲除抑制海马神经发生，LXR激动剂持续增加AD小鼠海马齿回RGLs的数量，提示LXRβ具有维持AD小鼠海马内RGLs数量，促进海马持续神经发生的作用，这一作用是否通过有效调控RGLs激活与静息之间的平衡而实现，其分子机制如何？目前尚不清楚。本课题采用LXRβ敲除与双转基因AD小鼠杂交，分析LXRβ对AD小鼠海马齿回RGLs激活与静息之间平衡的调控。SIRT1慢病毒感染检测LXRβ去乙酰化对AD小鼠海马神经发生及RGLs维持的调控；采用染色质免疫沉淀技术检测LXRβ对SIRT1下游Hes1与Ngn2的转录调节及LXRβ去乙酰化对P27（Kip1） 和Ngn2的调节，阐明LXRβ调控AD小鼠海马持续神经发生的机制，为自修复策略治疗AD提供理论依据。

Abnormal neurogenesis induced by depletion of f radial glia like cells (RGLs) in the dentate gyrus of hippocampus is considered to be a key factor related to dysfunction of learning and memory in the Alzheimer's disease (AD).Our previous study has demonstrated that loss of LXRβ inhibited adult hippocampus neurogenesis, whereas the number of RGLs in the dentate gyrus was increased in the AD mice pretreatment with LXR　agonist.These indicate that LXRβ is propbably involved in the maintaining the number of RGLs in the hippocampal dentate gyrus of AD mice, and thereby contributed to continuous hippocampus neurogenesis.Whether the modulating roles of LXRβ in the RGLs maintaining and continuous neurogenesis are related to the balance of resting and activation of RGLs , and the underlying mechanism has not been well explored.In the present study, the modulating roles of LXRβ involved in the the balance of resting and activation of RGLs in the AD mice hippocampus will be investigated with LXRβ knockout and AD double transgenic mice.SIRT1 lentivirus infection will be used to detect the effect of LXRβ deacetylation on the modulation of hippocampus neurogenesis and RGLs maintaing in the AD mice. A chromatin precipitation will be used to detect LXRβ modulation the Hes1 and Ngn2 transcription regulation of SIRT1 downstream. The effect of LXRβ deacetylation on the expression of P27 Kip1 and Ngn2 will be detected in the cultured hippcampal neural stem cell . It will clarify the underlying mechanism of LXRβ in the regulation of continued adult hippocampal neurogenesis in the AD mice, and therefore provide a theoretical basis for self-repair strategy to treat AD.