Astrocytic expression of HIV-1 viral protein R in the hippocampus causes chromatolysis, synaptic loss and memory impairment.
Astrocytic expression of HIV-1 viral protein R in the hippocampus causes chromatolysis, synaptic loss and memory impairment.
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DOI：
10.1186/1742-2094-11-53
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发表时间：
2014-03-22
影响因子：
9.3
通讯作者：
Noel RJ Jr
中科院分区：
文献类型：
--
作者：
Torres L;Noel RJ Jr
艾滋病毒感染者发生神经系统异常的风险增加。HIV通过宿主细胞因子和单个病毒蛋白诱导神经毒性。这些蛋白质中的一些包括病毒蛋白R（Vpr）促进免疫激活和神经元损伤。已知Vpr促进培养的大鼠海马神经元的细胞死亡并抑制轴突生长。行为研究有限，并建议在Vpr的存在下活动过度。因此，Vpr可能在海马功能丧失中起作用。本研究的目的是确定海马星形胶质细胞产生HIV-1 Vpr导致神经功能缺损和记忆障碍的能力。我们测试了大鼠在海马输注表达HIV-1 Vpr的星形胶质细胞后在新目标和新位置任务中的表现。突触素免疫反应和尼氏染色检测突触损伤和形态学变化。与表达绿色荧光蛋白（GFP）的对照组大鼠相比，注射Vpr的大鼠表现出受损的新位置和新物体识别。这种损害与海马CA3区突触素免疫反应性显著降低相关，表明HIV-1 Vpr治疗动物的突触损伤。此外，尼氏染色显示Vpr组神经元染色质溶解的形态学变化。Vpr诱导的神经元损伤和突触丢失表明，神经元功能障碍引起的空间和识别记忆缺陷中发现的Vpr输注动物。在这项研究中，我们证明，在海马星形胶质细胞产生的HIV-1 Vpr损害海马依赖性学习。这些数据表明Vpr是一种神经毒素，即使在病毒复制有限的条件下，也可能导致HIV-1感染者的学习障碍。
HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cell death of cultured rat hippocampal neurons and suppresses axonal growth. Behavioral studies are limited and suggest hyperactivity in the presence of Vpr. Thus Vpr may play a role in hippocampal loss of function. The purpose of this study is to determine the ability of HIV-1 Vpr production by astrocytes in the hippocampus to cause neurological deficits and memory impairments. We tested the performance of rats in novel object and novel location tasks after hippocampal infusion with astrocytes expressing HIV-1 Vpr. Synaptic injury and morphological changes were measured by synaptophysin immunoreactivity and Nissl staining. Vpr-infused rats showed impaired novel location and novel object recognition compared with control rats expressing green fluorescent protein (GFP). This impairment was correlated with a significant decrease in synaptophysin immunoreactivity in the hippocampal CA3 region, suggesting synaptic injury in HIV-1 Vpr-treated animals. In addition, Nissl staining showed morphological changes indicative of neuronal chromatolysis in the Vpr group. The Vpr-induced neuronal damage and synaptic loss suggest that neuronal dysfunction caused the spatial and recognition memory deficits found in the Vpr-infused animals. In this study, we demonstrate that HIV-1 Vpr produced by astrocytes in the hippocampus impairs hippocampal-dependent learning. The data suggest Vpr is a neurotoxin with the potential to cause learning impairment in HIV-1 infected individuals even under conditions of limited viral replication.
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影响因子：
3.2
作者：
Ferrucci, Adriano;Nonnemacher, Michael R.;Wigdahl, Brian
通讯作者：
Wigdahl, Brian
影响因子：
6.1
作者：
Chompre G;Cruz E;Maldonado L;Rivera-Amill V;Porter JT;Noel RJ Jr
通讯作者：
Noel RJ Jr
影响因子：
11.2
作者：
Giometto, B;An, SF;Scaravilli, F
通讯作者：
Scaravilli, F
影响因子：
11.2
作者：
Churchill, Melissa J.;Wesselingh, Steven L.;Gorry, Paul R.
通讯作者：
Gorry, Paul R.
影响因子：
6.2
作者：
Borjabad, Alejandra;Brooks, Andrew I.;Volsky, David J.
通讯作者：
Volsky, David J.