Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection.
Neuropsychological, Neurovirological and Neuroimmune Aspects of Abnormal GABAergic Transmission in HIV Infection.
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DOI：
10.1007/s11481-016-9652-2
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Gelman B
中科院分区：
文献类型：
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作者：
Buzhdygan T;Lisinicchia J;Patel V;Johnson K;Neugebauer V;Paessler S;Jennings K;Gelman B
在联合抗逆转录病毒治疗（cART）有效抑制病毒复制的患者中，HIV相关神经认知障碍（HAND）的患病率仍然很高。据报道，艾滋病毒感染患者的几种神经递质系统异常，包括抑制性GABA能系统，该系统介导神经元加工的微调，并在认知功能中发挥重要作用。为了阐明异常GABA能传递在HAND中的作用，在449例患有和不患有HAND的HIV感染患者的人脑标本中测定了GABA能标记物的表达。使用实时聚合酶链反应，免疫印迹和免疫组化，我们发现，GABA能标记物显着减少，在大多数部门的大脑新皮层，新纹状体，和小脑的HIV感染者。额叶新皮层GABA能表达低与内皮细胞标记物多巴胺受体2型（DRD 2L）和前脑啡肽原（PENK）mRNA的高表达显著相关，并且与语言流畅性任务的较差表现相关。在低GABA能mRNA和脑中HIV-1 RNA浓度、cART病史或HIV脑炎之间未发现显著相关性。不存在受影响GABA能神经元神经变性的病理学证据。我们的结论是异常低表达的GABA能标记物是普遍存在于HIV-1感染的患者。与其他神经递质系统，包括多巴胺能传递和内皮细胞标志物的相互关系提供了额外的支持，建议突触可塑性和脑血管异常参与HAND病毒抑制患者。本文的在线版本（doi：10.1007/s11481-016-9652-2）包含补充材料，可供授权用户使用。
The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients with effective suppression of virus replication by combination antiretroviral therapy (cART). Several neurotransmitter systems were reported to be abnormal in HIV-infected patients, including the inhibitory GABAergic system, which mediates fine-tuning of neuronal processing and plays an essential role in cognitive functioning. To elucidate the role of abnormal GABAergic transmission in HAND, the expression of GABAergic markers was measured in 449 human brain specimens from HIV-infected patients with and without HAND. Using real-time polymerase chain reaction, immunoblotting and immunohistochemistry we found that the GABAergic markers were significantly decreased in most sectors of cerebral neocortex, the neostriatum, and the cerebellum of HIV-infected subjects. Low GABAergic expression in frontal neocortex was correlated significantly with high expression of endothelial cell markers, dopamine receptor type 2 (DRD2L), and preproenkephalin (PENK) mRNAs, and with worse performance on tasks of verbal fluency. Significant associations were not found between low GABAergic mRNAs and HIV-1 RNA concentration in the brain, the history of cART, or HIV encephalitis. Pathological evidence of neurodegeneration of the affected GABAergic neurons was not present. We conclude that abnormally low expression of GABAergic markers is prevalent in HIV-1 infected patients. Interrelationships with other neurotransmitter systems including dopaminergic transmission and with endothelial cell markers lend added support to suggestions that synaptic plasticity and cerebrovascular anomalies are involved with HAND in virally suppressed patients. The online version of this article (doi:10.1007/s11481-016-9652-2) contains supplementary material, which is available to authorized users.