Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis.
Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis.
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DOI：
10.1007/s11481-012-9345-4
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发表时间：
2012-09
影响因子：
6.2
通讯作者：
Soukup, Vicki M.
中科院分区：
文献类型：
--
作者：
Gelman, Benjamin B.;Lisinicchia, Joshua G.;Chen, Tianshen;Johnson, Kenneth M.;Jennings, Kristofer;Freeman, Daniel H., Jr.;Soukup, Vicki M.
关键词：
HIV 脑炎 (HIVE) 患者的额叶新皮质会发生突触结构的变化，并可能导致 HIV 相关的神经认知障碍 (HAND)。进行了尸检调查，以确定 HIVE 或 HAND 受试者的背外侧前额皮质 (DLPFC) 中参与突触传递的 mRNA 是否受到干扰。与 67 名 HIV 阴性受试者相比，在 446 份 HIV-1 感染者脑样本样本中，阿片类神经递质前脑啡肽原 mRNA (PENK) 的表达显着降低。 DLPFC PENK 降低在 HIVE 患者和/或干扰素调节因子 1 mRNA (IRF1) 表达增加的受试者中最为明显。 2 型多巴胺受体 mRNA (DRD2L) 显着降低，但在同一组 PENK 失调的受试者中却没有显着降低。 DRD2L 下调主要发生在没有 HIVE 或神经认知障碍的受试者中。患有神经认知障碍的受试者通常无法显着下调 DRD2L，并且 IRF1 表达异常高。结论：在 HIV 感染者中，额叶新皮质中的突触前脑啡肽原和 DRD2L 的失调可能会发生在有或没有神经认知障碍的情况下。前额皮质中 DRD2L 的下调与更有利的神经心理学和神经病理学结果相关；未能下调 DRD2L 的效果明显较差。 PENK 下调在神经病理学上与 HIVE 相关，但与神经心理学结果无关。从药效学角度模拟内源性突触可塑性可以增强突触调节并改善艾滋病毒/艾滋病的神经心理学和神经病理学结果。
Changes in synapse structure occur in frontal neocortex with HIV encephalitis (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A postmortem survey was conducted to determine if mRNAs involved in synaptic transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin mRNA (PENK) was significantly decreased in a sampling of 446 brain specimens from HIV-1 infected people compared to 67 HIV negative subjects. Decreased DLPFC PENK was most evident in subjects with HIVE and/or increased expression of interferon regulatory factor 1 mRNA (IRF1). Type 2 dopamine receptor mRNA (DRD2L) was decreased significantly, but not in the same set of subjects with PENK dysregulation. DRD2L downregulation occurred primarily in the subjects without HIVE or neurocognitive impairment. Subjects with neurocognitive impairment often failed to significantly downregulate DRD2L and had abnormally high IRF1 expression. Conclusion: Dysregulation of synaptic preproenkephalin and DRD2L in frontal neocortex can occur with and without neurocognitive impairment in HIV-infected people. Downregulation of DRD2L in the prefrontal cortex was associated with more favorable neuropsychological and neuropathological outcomes; the failure to downregulate DRD2L was significantly less favorable. PENK downregulation was related neuropathologically to HIVE, but was not related to neuropsychological outcome independently. Emulating endogenous synaptic plasticity pharmacodynamically could enhance synaptic accommodation and improve neuropsychological and neuropathological outcomes in HIV/AIDS.
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影响因子：
2.9
作者：
Dafny, N;PrietoGomez, B;ReyesVazquez, C
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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