Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

Abstract

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.

Profiling of extracellular vesicle‐bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates

“…Previous studies have identified the pancreas, liver, intestine, brain, and heart to have altered miRNA expression with EtOH exposure (Natarajan et al, 2015). Further, studies have identified liver‐derived EV‐bound miRNA‐122 and let‐7f as indicators of alcohol‐induced liver injury (Odegaard et al, 2020). While it is known that miRNA packaging in EVs is selective and can have targeted effects on recipient cells, many of the functional mechanisms and downstream impacts of these processes remain elusive (Groot & Lee, 2020; Valadi et al, 2007a).…”

Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates

“…The copyright holder for this preprint (which this version posted July 29, 2021. ; https://doi.org/10.1101/2021.07.28.454223 doi: bioRxiv preprint 9 brain, and heart to have altered miRNA expression with ethanol exposure (34). Further, studies have identified liver-derived EV-bound miRNA 122 and let7f as indicators of alcohol-induced liver injury (35). While it is known that miRNA packaging in EVs is selective and can have targeted effects on recipient cells, many of the functional mechanisms and downstream impacts of these processes remain elusive (36,37).…”

Generational Effects of Opioid Exposure

“…Morphine is a potent analgesic primarily used in hospitals to combat severe pain. While morphine may be effective for pain relief, there are potential adverse side effects such as tolerance and addiction as well as molecular alterations [37]. Morphine's powerful analgesic effects stem from its role as an opioid receptor agonist.…”