Emergency Department, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou 061001, Hebei, China.
Cangzhou Medical College, Higher Education Area, the West of Yingbin Avenue, Yunhe District, Cangzhou 061001, Hebei, China.
Mol Cell Neurosci. 2018 Apr;88:158-166. doi: 10.1016/j.mcn.2018.02.002. Epub 2018 Feb 3.
Traumatic brain injury (TBI) has been associated with an increased risk for neurodegenerative diseases, and Tau spread and accumulation might be one of the mechanisms underlying this process. Exosomes were speculated to be a vehicle for spreading Tau in neurodegenerative diseases. The present study sought to investigate the effect of exosome associated Tau after TBI. C57BL/6J mice were subjected to controlled cortical impact injury and the levels of total and phosphorylated Tau in exosomes were measured. Then we isolated exosomes from wildtype and Tau-knockout mice after TBI. These exosomes were either added to primary cultured neurons to evaluate the toxicity, or injected into brains of mice subjected to TBI to evaluate the effect on brain functions. The levels of total and phosphorylated Tau in exosomes after TBI were significantly elevated. TBI derived exosomes displayed toxicity in primary neuron cultures, exacerbated TBI induced LTP (long-term potentiation) impairment and exacerbated motor and cognitive impairments after TBI. The exosome-associated Tau pathology was one of the mechanisms underlying the long-term neurodegenerative effect after TBI.
创伤性脑损伤（TBI）与神经退行性疾病的风险增加有关，而 Tau 的扩散和积累可能是这一过程的机制之一。外泌体被推测是神经退行性疾病中 Tau 扩散的载体。本研究旨在探讨 TBI 后与外泌体相关的 Tau 的影响。将 C57BL/6J 小鼠进行皮质撞击伤，测量外泌体中总 Tau 和磷酸化 Tau 的水平。然后，我们从 TBI 后的野生型和 Tau 敲除小鼠中分离出外泌体。将这些外泌体添加到原代培养的神经元中以评估其毒性，或注射到 TBI 小鼠的大脑中以评估其对脑功能的影响。TBI 后外泌体中总 Tau 和磷酸化 Tau 的水平显著升高。TBI 衍生的外泌体在原代神经元培养物中表现出毒性，加重了 TBI 诱导的 LTP（长时程增强）损伤，并加重了 TBI 后的运动和认知障碍。外泌体相关的 Tau 病理学是 TBI 后长期神经退行性效应的机制之一。
