Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons
Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons
复制标题
脑缺血损伤诱导丝切蛋白杆形成，导致神经元突触功能障碍
DOI：
10.1177/0271678x18785567
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发表时间：
2018-06
影响因子：
6.3
通讯作者：
Yun Wang
中科院分区：
文献类型：
--
作者：
Liang Shu;Ben Chen;Bin Chen;Hai Xu;Guoxiang Wang;Yian Huang;Yingya Zhao;Hui Gong;Min Jiang;Lidian Chen;Xu Liu;Yun Wang
缺血性脑卒中不仅引起梗死区神经元死亡，而且引起梗死周围存活神经元的结构和功能损伤。在本研究中，我们首次在体内缺血性脑卒中动物模型的神经元中发现了cofilin棒，一种病理性的杆状聚集物，并诱导神经元损伤。Cofilin杆仅在大脑中动脉闭塞再灌注（MCAO-R）大鼠脑同侧形成，在梗死周围区密度最高。我们的实时活细胞成像、免疫染色和膜片钳研究表明，神经元中cofilin棒的形成导致树突状线粒体运输失败，以及突触结构和功能的损害。LIM激酶的过表达或其上游调节因子Rho的激活，抑制了缺血诱导的cofilin杆的形成，并对培养神经元和MCAO-R大鼠模型的突触功能和结构损伤均有保护作用。综上所述，我们的研究结果揭示了缺血性卒中引起的梗死周围区神经元损伤的新机制，并为保护神经元结构和功能免受脑缺血损伤提供了潜在的靶点。
Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult.
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影响因子：
21.3
作者：
Gohla, A;Birkenfeld, J;Bokoch, GM
通讯作者：
Bokoch, GM
DOI：
10.1523/jneurosci.4681-08.2009
发表时间：
2009-06-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Shi Y;Pontrello CG;DeFea KA;Reichardt LF;Ethell IM
通讯作者：
Ethell IM
影响因子：
25
作者：
Gu, Jiaping;Lee, Chi Wai;Fan, Yanjie;Komlos, Daniel;Tang, Xin;Sun, Chicheng;Yu, Kuai;Hartzell, H. Criss;Chen, Gong;Bamburg, James R.;Zheng, James Q.
通讯作者：
Zheng, James Q.
影响因子：
16
作者：
Andrianantoandro, Ernesto;Pollard, Thomas D.
通讯作者：
Pollard, Thomas D.
影响因子：
8.3
作者：
Rikitake, Y;Kim, HH;Liao, JK
通讯作者：
Liao, JK