A comprehensive study to delineate the role of an extracellular vesicle-associated microRNA-29a in chronic methamphetamine use disorder

Authors

• Subhash Chand, University of Nebraska Medical Center
• Austin Gowen, University of Nebraska Medical Center
• Mason Savine, University of Nebraska Medical Center
• Dalia Moore, University of Nebraska Medical Center
• Alexander Clark, University of Nebraska Medical Center
• Wendy Huynh, University of Nebraska–Lincoln
• Niming Wu, University of Nebraska Medical Center
• Katherine Odegaard, University of Nebraska Medical Center
• Lucas Weyrich, Midland University
• Rick A. Bevins, University of Nebraska–LincolnFollow
• Howard S. Fox, University of Nebraska Medical Center
• Gurudutt Pendyala, University of Nebraska Medical Center
• Sowmya V. Yelamanchili, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

2021

Citation

J ExtracellVesicles. 2021;10:e12177. wileyonlinelibrary.com/journal/jev2 https://doi.org/10.1002/jev2.12177

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2021 TheAuthors. Journal of Extracellular Vesicles published byWiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles

Abstract

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR- 29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EVassociated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti-inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR-29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma fromMUDsubjects, we provide translational evidence that EV-miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EVassociated miR-29a-3p plays a crucial role in MUD and might be used as a potential blood-based biomarker for detecting chronic inflammation and synaptic damage.