The small RNA sequencing data of EcoHIV-infected mouse brain tissue derived extracellular vesicles. The small RNA sequencing data of EcoHIV-infected mouse brain tissue derived extracellular vesicles

Given the nefarious role that Extracellular vesicles (EVs) can play in disease pathogenesis, there is a growing interest in examining the contents of EVs in many disorders, including depression, HIV, and HIV-Associated Neurocognitive Disorder (HAND). EVs are particularly enriched with miRNA, and the nervous system expresses approximately 70% of all miRNA. miRNA typically regulate gene expression via degrading or suppressing mRNA translation, and these small non-coding RNAs, which are thought to be shuttled between cells via EVs, have been implicated in a host of diseases and conditions, including depression and cognitive decline. To our knowledge, however, this is the first study to examine brain-derived (bd) EV miRNA content in a preclinical model of HIV-associated CI and depression. We report 4 miRNAs, including miR-429-3p, miR-200c-3p, miR-183-5p, and miR-200b-3p, that are significantly upregulated in bdEVs of EcoHIV-infected mice and normalized by novel treatment. Overall design: People living with HIV (PLWHIV) have significantly higher rates of cognitive impairment (CI) and major depressive disorder (MDD) versus the general population. The enzyme neutral sphingomyelinase 2 (nSMase2) is involved in the biogenesis of ceramide and extracellular vesicles (EVs), both of which are dysregulated in PLWHIV, CI, and MDD. Here we evaluated EcoHIV-infected mice for behavioral abnormalities relevant to depression and cognition deficits, and assessed the behavioral and biochemical effects of nSMase2 inhibition. RNA was extracted from EVs separated from the prefrontal cortex (PFC) or hippocampus (HPC) of control and EcoHIV-infected mice with/without nsMase2 inbitor treatment. Given the relatively low yield of EVs, samples were pooled from 6-8 mice for small RNA sequencing.

鉴于细胞外囊泡（Extracellular vesicles, EVs）在疾病发病机制中所扮演的有害角色，学界对多种疾病中外囊泡内容物的研究兴趣与日俱增，这些疾病包括抑郁症、人类免疫缺陷病毒（HIV）感染以及HIV相关神经认知障碍（HIV-Associated Neurocognitive Disorder, HAND）。细胞外囊泡尤其富含微RNA（microRNA, miRNA），而神经系统表达的微RNA占所有微RNA的约70%。微RNA通常通过降解信使RNA（messenger RNA, mRNA）或抑制其翻译来调控基因表达；这类小型非编码RNA被认为可通过细胞外囊泡在细胞间穿梭，现已被证实与包括抑郁症、认知衰退在内的多种疾病及病症密切相关。然而据我们所知，本研究首次针对HIV相关认知障碍（cognitive impairment, CI）与抑郁症的临床前模型，探究了脑源性（brain-derived, bd）细胞外囊泡的微RNA含量。本研究鉴定出4种在EcoHIV感染小鼠的脑源性细胞外囊泡中显著上调的微RNA，分别为miR-429-3p、miR-200c-3p、miR-183-5p以及miR-200b-3p，且新型治疗可使其表达恢复正常。研究整体设计：相较于普通人群，人类免疫缺陷病毒感染者（People living with HIV, PLWHIV）的认知障碍与重度抑郁症（major depressive disorder, MDD）患病率显著更高。中性鞘磷脂酶2（neutral sphingomyelinase 2, nSMase2）参与神经酰胺与细胞外囊泡的生物发生，而这两类物质在人类免疫缺陷病毒感染者、认知障碍患者及重度抑郁症患者体内均存在失调情况。本研究对EcoHIV感染小鼠开展了与抑郁症及认知缺陷相关的行为学异常评估，并考察了中性鞘磷脂酶2抑制的行为学与生化效应。我们从对照组与经/未经中性鞘磷脂酶2抑制剂处理的EcoHIV感染小鼠的前额叶皮层（prefrontal cortex, PFC）或海马体（hippocampus, HPC）分离得到细胞外囊泡，并从中提取RNA。鉴于细胞外囊泡的提取量相对较低，本研究将6~8只小鼠的样本混合后进行小RNA测序。