Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?
Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?
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趋化因子 CCL2 增强大鼠海马切片中 NMDA 受体介导的兴奋性突触后电流 - HIV-1 相关神经病的潜在机制？
DOI：
10.1007/s11481-016-9660-2
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发表时间：
2016-03
影响因子：
6.2
通讯作者：
Xiong Huangui
中科院分区：
文献类型：
--
作者：
Zhou Yan;Tang Hongmei;Xiong Huangui
人类免疫缺陷病毒1型（HIV-1）感染的单核吞噬细胞（脑巨噬细胞和小胶质细胞）释放促炎细胞因子和趋化因子。已在HIV-1感染个体的血清和脑脊液（CSF）中检测到趋化因子CC基序配体2（CCL 2，以前称为单核细胞趋化蛋白-1）水平升高，并且CSF中升高的CCL 2与HIV-1相关的神经认知障碍相关。为了了解升高的CCL 2如何诱导HIV-1相关神经病变，我们使用全细胞膜片记录技术研究了CCL 2对大鼠海马脑片CA 1区兴奋性突触后电流（EPSC）的影响。分离AMPA受体（AMPAR）介导的EPSC（EPSCAMPAR）和N-甲基-D-天冬氨酸（NMDA）受体（NMDAR）介导的EPSC（EPSCNMDAR）。浴用CCL 2可使EPSC、EPSCAMPAR和EPSCNMDAR的振幅显著增强。进一步的研究表明，CCL 2增强NMDAR亚型NR 2A介导的EPSC（EPSCNR 2AR）和NR 2B介导的EPSC（EPSCNR 2BR）。为了确定作用部位，我们记录了在沐浴应用CCL 2之前和期间的自发迷你EPSC（mEPSC）。我们的结果表明，CCL 2缩短事件间间期（IEI），增加mEPSC的频率，而不改变振幅，表明CCL 2的突触前位点的行动。CCL 2还被发现损伤原代大鼠海马神经元培养物和海马脑片CA 1区的神经元树突。CCL 2相关的神经元和树突损伤被特定的NMDAR拮抗剂或CCR 2受体拮抗剂阻断，表明CCL 2相关的神经损伤通过NMDAR和/或CCR 2受体介导。总之，这些结果表明CCL 2可能在HIV-1相关的神经病理学中发挥潜在作用。
Human immunodeficiency virus type 1 (HIV-1)-infected mononuclear phagocytes (brain macrophages and microglial cells) release proinflammatory cytokines and chemokines. Elevated levels of chemokine CC motif ligand 2 (CCL2, known previously as monocyte chemoattractant protein-1) have been detected in serum and cerebrospinal fluid (CSF) of HIV-1-infected individuals and the raised CCL2 in the CSF correlates with HIV-1-associated neurocognitive disorders. To understand how elevated CCL2 induces HIV-1-associated neuropathy, we studied effects of CCL2 on excitatory postsynaptic current (EPSCs) in the CA1 region of rat hippocampal brain slices using whole-cell patch recording techniques. The AMPA receptor (AMPAR)-mediated EPSC (EPSCAMPAR) and N-Methyl-D-aspartate (NMDA) receptor (NMDAR)-mediated EPSCs (EPSCNMDAR) were isolated pharmacologically. Bath application of CCL2 produced a significant enhancement of the amplitudes of EPSCs, EPSCAMPARand EPSCNMDAR. Further studies revealed that CCL2 potentiated NMDAR subtype NR2A-mediated EPSC (EPSCNR2AR) and NR2B-mediated EPSC (EPSCNR2BR). To determine the site of action, we recorded spontaneous mini EPSCs (mEPSC) before and during bath application of CCL2. Our results showed that CCL2 decreased inter event interval (IEI) and increased the frequency of mEPSCs without change on the amplitude, suggesting a presynaptic site of CCL2 action. CCL2 was also found to injure primary rat hippocampal neuronal cultures and neuronal dendrites in the CA1 region of hippocampal slices. The CCL2-associated neuronal and dendritic injuries were blocked by a specific NMDAR antagonist or by a CCR2 receptor antagonist, indicating that CCL2-associated neural injury was mediated via NMDARs and/or CCR2 receptors. Taken together, these results suggest a potential role CCL2 may play in HIV-1-associated neuropathology.
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影响因子：
5.3
作者：
Fan X;Jin WY;Wang YT
通讯作者：
Wang YT
影响因子：
4.7
作者：
Blair, Robert E.;Deshpande, Laxmikant S.;Sombati, Sompong;Elphick, Maurice R.;Martin, Billy R.;DeLorenzo, Robert J.
通讯作者：
DeLorenzo, Robert J.
影响因子：
6
作者：
Fujikawa, Denson G.
通讯作者：
Fujikawa, Denson G.
影响因子：
2.6
作者：
B. Shiramizu;E. Lau;A. Tamamoto;J. Uniatowski;D. Troelstrup
通讯作者：
B. Shiramizu;E. Lau;A. Tamamoto;J. Uniatowski;D. Troelstrup
影响因子：
4.7
作者：
Wen-tao Wang;Guoyan Pan;Zi-Yang Zhang;Zhanwei Suo;Xian Yang;Xiao-Dong Hu
通讯作者：
Wen-tao Wang;Guoyan Pan;Zi-Yang Zhang;Zhanwei Suo;Xian Yang;Xiao-Dong Hu