突触相关的tau蛋白传播在脑外伤导致认知功能障碍中的作用及其机制研究

Traumatic brain injury (TBI) is the primacy cause of death and disability among the youth. Unfortunately, even though survive from TBI, 80% of patients will face the cognitive impairment, which result in heavy family and social burden. However, there was no effective strategy for prevention, for the mechanism of TBI induced cognitive impairment was still unknown. Tau is correlated to the cognitive impairment, for its hyperphosphorylation is the key pathway for Alzheimer’s disease, Chronic traumatic encephalopathy, Parkinson's Disease and so on. Our previous studies have shown that rats suffered TBI had significant cognitive decline and tau of the brain tissues exhibited hyperphosphorylation. According to these, we speculated that the hyperphosphorylation of tau probably was the mechanism of TBI induced cognitive impairment. Traumatic axonal injury leads to the tau detaches from the microtubule in the damage area. Tau can then lead into a pathological pathway where it can hyperphosphorylate, adopt a soluble oligomeric conformation and aggregate. How does the local reaction develop to a large area hyperphosphorylation, which causes the cognitive impairment? Lines of researches have indicated that tau could propagate in the brain, just like the Prion. Therefore, the propagation was associated with synapse. In this context, we aimed to clear the relationship between hyperphosphorylated tau and TBI induced cognitive impairment, investigate whether tau propagate via synapse, as well as the morphology of tau during the propagation. It may not only provide novel insights for TBI induced cognitive impairment, but also explore new potential strategies for prevention and treatment.

脑外伤（TBI）是青年人首位的致残致死原因，而幸存者中高达80%的人将面临认知功能障碍的困境，给社会造成了沉重的负担。但由于其机制不明，目前仍无有效的防治手段。Tau蛋白与认知功能障碍密切相关，我们的前期实验证实，TBI可致大鼠认知功能减退，并在大鼠脑组织内发现tau蛋白过度磷酸化。据此推测，tau蛋白的过度磷酸化可能是TBI后认知功能障碍的发病机制。TBI后轴突损伤，导致损伤侧tau蛋白游离并过度磷酸化。那么，这一局部反应是如何转变为全脑tau蛋白过度磷酸化，最终引起认知功能障碍的呢？近年来，诸多证据显示tau蛋白可在脑内进行传播，且与突触相关。为此，本课题利用形态学、行为学等方法，明确tau蛋白过度磷酸化与TBI后认知功能障碍的关系，研究TBI后tau蛋白是否经突触传播，并观察该过程中tau蛋白的形态。旨在为TBI后认知功能障碍的发病机制研究提供新思路，为其防治策略提供潜在的干预靶点。

脑损伤是青年人首位的致残致死原因，而幸存者中高达80%的人将面临认知功能障碍的困境，给社会造成了沉重的负担。为此，本课题利用形态学、行为学等方法，明确其与脑损伤后认知功能障碍的关系，发现脑外伤后大鼠会出现认知功能障碍为主的行为学改变，并且在大鼠损伤脑组织内发现tau蛋白的磷酸化程度明显增高，且另一种密切相关的APP蛋白表达也明显增高，这一过程可能有突触相关蛋白介导。