HIV-1 Glycoprotein 120 Enhancement of N-Methyl-D-Aspartate NMDA Receptor-Mediated Excitatory Postsynaptic Currents: Implications for HIV-1-Associated Neural Injury.
HIV-1 Glycoprotein 120 Enhancement of N-Methyl-D-Aspartate NMDA Receptor-Mediated Excitatory Postsynaptic Currents: Implications for HIV-1-Associated Neural Injury.
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HIV-1 糖蛋白 120 N-甲基-D-天冬氨酸 NMDA 受体介导的兴奋性突触后电流的增强：对 HIV-1 相关神经损伤的影响
DOI：
10.1007/s11481-016-9719-0
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Xiong H
中科院分区：
文献类型：
--
作者：
Zhou Y;Liu J;Xiong H
HIV-1包膜糖蛋白120（gp 120）在HIV-1诱导的神经损伤和HIV-1相关性痴呆（HAND）的发病机制中起重要作用。已经提出了gp 120诱导的神经毒性的多种途径，其中包括N-甲基-D-天冬氨酸受体（NMDAR）的激活。已经显示gp 120引起神经元损伤或死亡，并且gp 120转基因小鼠表现出与HAND的神经相似性，所有这些都可以被NMDAR拮抗剂阻断或减弱。一些证据表明，活化的NMDAR的亚型和位置是NMDAR生理学性质的关键决定因素。为了研究gp 120影响NMDAR的亚型和位置，我们通过“盲”全细胞斑片记录研究了gp 120对大鼠海马脑片CA 1区NMDAR亚型介导的EPSC的影响。我们的研究结果表明，浴应用gp 120增加NR 2A和NR 2B介导的EPSCs可能通过突触前机制，与NR 2B介导的EPSCs更强的影响。相反，gp 120未能增强AMPA受体介导的EPSC。Ca ~（2+）显像结果显示，gp 120可增强谷氨酸诱导的海马神经元胞内Ca ~（2+）浓度升高，但这种作用可被NMDAR拮抗剂阻断，而不能被AMPA受体拮抗剂阻断，表明gp 120通过NMDAR诱导Ca ~（2+）内流。进一步的研究表明gp 120增加了突触外NR 2BRs介导的EPSC。两者合计，这些结果表明，gp 120相互作用与NR 2A和NR 2B亚型的NMDARs与突触外NR 2B，这可能涉及的作用NR 2B可能发挥HIV-1相关的神经病理学的主要行动。
It is widely accepted that human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) plays an important role in HIV-1-induced neural injury and pathogenesis of HIV-1-associated dementia (HAND). Multiple pathways have been proposed for gp120-induced neurotoxicity, amongst is the activation of N-Methyl-D-Aspartate receptors (NMDARs). It has been shown that gp120 causes neuronal injury or death and gp120 transgenic mice exhibit neurological similarity to that of HAND, all of which can be blocked or attenuated by NMDAR antagonists. Several lines of evidence indicate the subtype and location of activated NMDARs are key determinants of the nature of NMDAR physiology. To examine the subtype and the location of NMDARs affected by gp120, we studied gp120 on subtype NMDAR-mediated EPSCs in the CA1 region of rat hippocampal slices through “blind” whole-cell patch recordings. Our results showed bath application of gp120 increased both NR2A- and NR2B-mediated EPSCs possibly via a presynaptic mechanism, with much stronger effect on NR2B-mediated EPSCs. In contrast, gp120 failed on enhancing AMPA receptor-mediated EPSCs. Ca2+ imaging studies revealed that gp120 potentiated glutamate-induced increase of intracellular Ca2+ concentration in rat hippocampal neuronal cultures which were blocked by a NMDAR antagonist, but not by an AMPA receptor antagonist, indicating gp120 induce Ca2+ influx through NMDARs. Further investigation demonstrated that gp120 increased the EPSCs mediated by extrasynaptic NR2BRs. Taken together, these results demonstrate that gp120 interacts with both NR2A and NR2B subtypes of NMDARs with a predominant action on the extrasynaptic NR2B, which may implicate a role NR2B may play in HIV-1-associated neuropathology.
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影响因子：
15.9
作者：
Banerjee A;Larsen RS;Philpot BD;Paulsen O
通讯作者：
Paulsen O
影响因子：
3.3
作者：
Barks, JDE;Liu, XH;Silverstein, FS
通讯作者：
Silverstein, FS
影响因子：
3.2
作者：
Heaton, Robert K.;Franklin, Donald R.;Ellis, Ronald J.;McCutchan, J. Allen;Letendre, Scott L.;LeBlanc, Shannon;Corkran, Stephanie H.;Duarte, Nichole A.;Clifford, David B.;Woods, Steven P.;Collier, Ann C.;Marra, Christina M.;Morgello, Susan;Mindt, Monica Rivera;Taylor, Michael J.;Marcotte, Thomas D.;Atkinson, J. Hampton;Wolfson, Tanya;Gelman, Benjamin B.;McArthur, Justin C.;Simpson, David M.;Abramson, Ian;Gamst, Anthony;Fennema-Notestine, Christine;Jernigan, Terry L.;Wong, Joseph;Grant, Igor
通讯作者：
Grant, Igor
影响因子：
2.9
作者：
GLOWA, JR;PANLILIO, LV;HILL, JM
通讯作者：
HILL, JM
DOI：
10.1073/pnas.96.14.8212
发表时间：
1999-07-06
影响因子：
11.1
作者：
Kaul, M;Lipton, SA
通讯作者：
Lipton, SA