Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1.
Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1.
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趋化因子受体 CX3CR1 介导缺血诱导的神经细胞死亡
DOI：
10.1038/s41598-017-18774-0
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发表时间：
2018-01-11
影响因子：
4.6
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Wang J;Gan Y;Han P;Yin J;Liu Q;Ghanian S;Gao F;Gong G;Tang Z
趋化因子fractalkine （CX3CL1）及其受体CX3CR1在脑卒中的病理生理中起重要作用。先前的研究主要集中在产生fractalkine的神经元和中枢神经系统中表达CX3CR1受体的小胶质细胞之间的旁分泌相互作用。最近的研究结果表明，CX3CR1受体在海马神经元中的功能表达，表明它们参与神经保护和神经退行性作用。采用小鼠永久性大脑中动脉闭塞（pMCAO）模型，探讨神经元CX3CR1在缺血性脑卒中神经退行性变中的作用。在pMCAO小鼠中，闭塞24小时后纹状体和海马中观察到CX3CR1水平升高，凋亡相关的形态学改变和Caspase 3阳性神经元细胞。缺血神经元中CX3CR1的上调与神经元凋亡细胞死亡有关。相比之下，CX3CR1缺陷小鼠缺血诱导的凋亡神经元细胞死亡减少。CX3CR1缺失小鼠培养的原代海马神经元通过阻断钙内流对谷氨酸诱导的兴奋性毒性的抵抗强于野生型小鼠。我们首次报道了神经元CXCR1介导缺血时神经元凋亡细胞死亡。我们的研究结果表明，调节CXCR1活性为中风提供了一种新的治疗策略。
The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke. Previous studies have focused on a paracrine interaction between neurons that produce fractalkine and microglia that express CX3CR1 receptors in the central nervous system. Recent findings have demonstrated the functional expression of CX3CR1 receptors by hippocampal neurons, suggesting their involvement in neuroprotective and neurodegenerative actions. To elucidate the roles of neuronal CX3CR1 in neurodegeneration induced by ischemic stroke, a mouse model of permanent middle cerebral artery occlusion (pMCAO) was employed. In the pMCAO mice, increased CX3CR1 levels, apoptosis-associated morphological changes, and Caspase 3-positive neuronal cells were observed in the striatum and in the hippocampus 24 hours after occlusion. Upregulation of CX3CR1 in ischemic neurons is associated with neuronal apoptotic cell death. In contrast, ischemia-induced apoptotic neuronal cell death was decreased in CX3CR1 deficient mice. Cultured primary hippocampal neurons obtained from CX3CR1 deficient mice were more resistant to glutamate-induced excitotoxicity by blocking calcium influx than those from wild-type mice. For the first time, we reported that neuronal CXCR1 mediates neuronal apoptotic cell death in ischemia. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for stroke.
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影响因子：
1.2
作者：
Seibenhener, Michael L.;Wooten, Marie W.
通讯作者：
Wooten, Marie W.
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
3.7
作者：
Dworzak J;Renvoisé B;Habchi J;Yates EV;Combadière C;Knowles TP;Dobson CM;Blackstone C;Paulsen O;Murphy PM
通讯作者：
Murphy PM