阿尔茨海默病（AD）是一种以记忆和认知损害为主要特征的神经系统退行性疾病，发病机理不明确，尚无有效治疗手段。目前尚不清楚各类干细胞及神经因子对于海马突触结构有何影响。4-6月龄5×FAD 小鼠出现海马依懒的行为异常，海马内乙酰胆碱转移酶活性下降。BDNF是神经突触塑形的关键因子并有助ASCs向神经元定向分化，且ASCs可通过血脑屏障。因此，本课题拟采用转染BDNF基因的ASCs 对4-6月龄5×FAD海马内移植，通过观察小鼠行为学、海马形态学及电生理学的改变，并通过免疫荧光检测synapsin、synaptophysin, GAP-43 、NEP及ChAT的表达，观察BDNF和ASCs对AD小鼠突触塑形影响，探讨其对海马神经元功能重建的形态学及生理学机制，为深入研究BDNF及ASCs改善AD病变的分子机制提供依据。

Pathologically, AD is characterized by the progressive accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles within the brain. Together, these pathologies lead to marked neuronal and synaptic loss and corresponding impairments in cognition. Current treatments, and recent clinical trials, have failed to modify the clinical course of AD; thus, the development of novel and innovative therapies is urgently needed. Recent studies have suggested that stem cell transplantation could serve as a potential therapeutic strategy to halt or ameliorate the inexorable disease progression. But it is unclear which types of stem cells and nerve factors work on synaptic structure. Acetylcholine transferase activity decreased in the hippocampus of 4-6 months age 5 × FAD mouse model of Alzheimer’s disease leading abnormal behavior. Due to BDNF is a key factor for the synaptic plasticity, improve ASCs differentiation into neurons, and also can through the blood brain barrier. In this project, We use ASCs designed to transient over-express BDNF, transplant into hippocampus of 4-6 months age 5xFAD mouse model of Alzheimer's disease to test animal model behavior; observe hippocampus structure, synaptic density, synapse formation, synapse plasticity, dendritic apine morphology by using TEM; evaluate the induction of LTP in CA1 area of hippocampus; observe the expression of synapsin, synaptophysin, GAP-43 , NEP and Choline acetyltransferase by immunofluorescence. The aim is to provide the molecular mechanism of BDNF and ASCs improving AD hippocampus for further study.