GSE182743
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.