肠道菌群稳态对阿尔兹海默症模型鼠认知和突触功能的调节机制研究

The homeostasis of gut bacteria was found to be majorly related to central nerve system diseases, and the appropriate maintaining homeostasis of gut bacteria was considered as a promising way to provent or even cure Alzheimer's disease. The applicant here has already established a novel Thy-1-YFP expressed AD mice model (3xTg:Thy1-YFP), through which model one could easily operate live imaging on mice cortex or even hippocampus to record neuronal synaptic dynamics or plasticity . Based on that novel mouse model and updated live imaging technique, the current proposal would elucidate the hypothesis "whether the homeostasis of gut bacteria have benifits on cognitive ability or synaptic function as well as the related mechanisms" through 3 aspects: 1. whether disrupted gut bacteria homeostasis is related with synaptic dysfunction or cognitive impairment; 2. whether administrating Lactobacillus plantarum and Bifidobacterium longum supplement on 3xTg:Thy1-YFP mice could regulate the homeostasis of gut bacteria in different ages and thus benefits synaptic dysfunction or cognitive impairment. 3. whether lipid metabolism dysfunction and intracellular Aβ accumulation involved in this process as important mechanisms. The current proposal would elucidate the significants and mechanisms of gut bacteria homeostasis on AD related synaptic dysfunction and cognitive impairment. This project should also raise solid evidences and breakthrough concepts for AD prevention and treatment.

肠道菌群稳态与神经疾病的关系日益受到研究者的重视，调节改善肠道菌群紊乱而实现阿尔兹海默症（AD）的防治是一个极具潜力的新研究实践方向。申请人前期已经成功培育了表达Thy-1启动子调控YFP荧光的AD模型鼠（3xTg:Thy1-YFP)，可以在皮层和海马区对突触形态功能进行持续性动态观察。以该系小鼠作为关键试验平台，以神经元突触的活体动态观察作为重要技术手段，本课题紧密围绕“调节肠道菌群稳态是否可以缓解AD模型鼠认知和突触功能障碍”这一问题，从以下3个方面展开研究：1.肠道菌群失调是否与AD模型鼠的突触功能和认知障碍相关；2.补充益生菌是否可以改善突触功能和认知障碍；3.脂类代谢紊乱和Aβ代谢异常是否作为重要因素，参与了肠道菌群失调所导致的突触功能损伤。本课题旨在阐明肠道菌群稳态在神经认知功能和AD病理过程中起到的重要作用和分子机制，为AD的防治提供坚实的实验基础与理论突破。

肠道菌群稳态与神经疾病的关系日益受到研究者的重视，调节改善肠道菌群紊乱而实现阿尔兹海默症（AD）的防治是一个极具潜力的新研究实践方向。在课题申请阶段，申请人计划从以下3个方面展开研究：1.探讨肠道菌群失调是否与AD模型鼠的突触功能和认知障碍相关；2.验证补充益生菌是否可以改善突触功能和认知障碍；3.探讨脂类代谢紊乱和Aβ代谢异常是否与肠道菌群失调所导致的突触功能损伤相关。本课题旨在阐明肠道菌群稳态在神经认知功能和AD病理过程中起到的重要作用和分子机制，为AD的防治提供创新的实验基础与理论突破。本课题目前取得的结果包括：通过对粪便的微生物mRNA组进行测序，本研究发现了AD动物确实存在肠道菌群分布异常。其次，通过对小鼠进行新型益生菌干预，本研究发现具有发明专利的新型益生菌配方“BIOCG”可以有效的改善AD模型鼠的认知行为能力和突触功能。最后，本研究发现免疫系统稳态的调节以及相应的Aβ代谢异常是肠道菌群调节突触功能的潜在机制。