Plasma microRNAs are associated with domain-specific cognitive function in people with HIV.
Plasma microRNAs are associated with domain-specific cognitive function in people with HIV.
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血浆microRNA与HIV感染者的领域特异性认知功能相关
DOI：
10.1097/qad.0000000000002966
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发表时间：
2021-09-01
期刊：
影响因子：
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通讯作者：
Rubin LH
中科院分区：
文献类型：
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作者：
Massanett Aparicio J;Xu Y;Li Y;Colantuoni C;Dastgheyb R;Williams DW;Asahchop EL;McMillian JM;Power C;Fujiwara E;Gill MJ;Rubin LH
认知障碍在接受抗逆转录病毒治疗（ART）的艾滋病毒感染者（PWH）中仍然很常见。PWH的临床表现和严重程度差异很大，这表明认知并发症的病理生理机制可能是复杂和多因素的。microRNA（miRNA）表达变化可能与认知有关，因为它们是参与免疫和应激反应以及神经元发育、可塑性和分化的基因调节剂。我们研究了PWH患者血浆miRNA表达变化与区域特异性和整体认知功能的关系。横断面观察研究33名在加拿大南阿尔伯塔诊所接受治疗的PWH完成了神经心理学（NP）测试和抽血。血浆miRNA提取后进行阵列杂交。使用随机森林分析来鉴定与认知相关的前10种上调和下调的miRNA。在认知领域中很少发现miRNA;然而，当miRNA明显与两个或三个领域相关时。值得注意的是，miR-127- 3 p与学习/记忆相关，miR-485- 5 p与运动功能相关，这些miRNA先前分别在阿尔茨海默氏症和帕金森氏症的CSF或血浆中鉴定。使用miRNET 2.0，一个通过基于网络的方法理解与认知相关的miRNA靶点（基因）的生物学相关性的软件平台，我们鉴定了与执行功能，学习/记忆和语言相关的信号传导，细胞周期和转录相关的基因。研究结果支持这样的想法，即在全球NP功能的背景下评估miRNA表达（或任何分子测量）可能会排除miRNA，这些miRNA可能是导致PWH中观察到的可变神经精神结局的域特异性机制的重要贡献者。
Cognitive impairment remains common in people with HIV(PWH) on antiretroviral therapy(ART). The clinical presentation and severity is highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA(miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons. We examined plasma miRNA expression changes in relation to domain-specific and global cognitive function in PWH. Cross-sectional observational study Thirty-three PWH receiving care at the Southern Alberta Clinic, Canada completed neuropsychological(NP) testing and blood draw. Plasma miRNA extraction was followed by array hybridization. Random forest analysis was used to identify the top 10 miRNAs upregulated and downregulated in relation to cognition. Few miRNAs were identified across cognitive domains; however, when evident a miRNA was only associated with two or three domains. Notably, miR-127-3p was related to learning/memory and miR-485-5p to motor function, miRNAs previously identified in CSF or plasma in Alzheimer’s and Parkinson’s, respectively. Using miRNET 2.0, a software-platform for understanding the biological relevance of the miRNA-targets (genes) relating to cognition through a network-based approach, we identified genes involved in signaling, cell cycle, and transcription relating to executive function, learning/memory, and language. Findings support the idea that evaluating miRNA expression (or any molecular measure) in the context of global NP function might exclude miRNAs that could be important contributors to the domain-specific mechanisms leading to the variable neuropsychiatric outcomes seen in PWH.