Zhao Zi-Ai, Ning Ya-Lei, Li Ping, Yang Nan, Peng Yan, Xiong Ren-Ping, Zhao Yan, Liu Dong, Zeng Xu-Jia, Chen Jiang-Fan, Zhou Yuan-Guo
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Trauma Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Behav Brain Res. 2017 Apr 14;323:146-153. doi: 10.1016/j.bbr.2017.02.002. Epub 2017 Feb 2.
A series of neurological and psychiatric symptoms occur after traumatic brain injury (TBI), with cognitive dysfunction being one of the most prominent sequela. Given that tau hyperphosphorylation is an important cause of cognitive impairment in patients of Alzheimer's disease, our present study detected the presence of hyperphosphorylated tau (p-tau), mainly at Ser404, in multiple brain regions, including the ipsilateral parietal cortex, contralateral hippocampus and prefrontal cortex, immediately after the injury in a mouse TBI model; these changes lasted for at least 4w. All of these brain regions play important roles in working memory. Hyperphosphorylated tau protein was primarily located in neurons and was accompanied by axonal injury and dendritic spine degeneration. Our study demonstrated that p-tau spreads gradually and selectively from the injured cortex to other brain regions after TBI and that all of the affected regions are part of the working memory circuit. These findings provide experimental support for the role of p-tau in cognitive impairment in the early phase after TBI.
创伤性脑损伤（TBI）后会出现一系列神经和精神症状，认知功能障碍是最突出的后遗症之一。鉴于tau蛋白过度磷酸化是阿尔茨海默病患者认知障碍的重要原因，我们目前的研究在小鼠TBI模型损伤后立即检测了多个脑区中主要位于Ser404的过度磷酸化tau（p-tau）的存在，这些脑区包括同侧顶叶皮层、对侧海马体和前额叶皮层；这些变化持续了至少4周。所有这些脑区在工作记忆中都起着重要作用。过度磷酸化的tau蛋白主要位于神经元中，并伴有轴突损伤和树突棘退化。我们的研究表明，TBI后p-tau从受损皮层逐渐选择性地扩散到其他脑区，并且所有受影响的区域都是工作记忆回路的一部分。这些发现为p-tau在TBI后早期认知障碍中的作用提供了实验支持。
