Open AccessA comprehensive study to delineate the role of an extracellular vesicle‐associated microRNA‐29a in chronic methamphetamine use disorder
Author(s) -
Chand Subhash,
Gowen Austin,
Savine Mason,
Moore Dalia,
Clark Alexander,
Huynh Wendy,
Wu Niming,
Odegaard Katherine,
Weyrich Lucas,
Bevins Rick A.,
Fox Howard S.,
Pendyala Gurudutt,
Yelamanchili Sowmya V.
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12177
Subject(s) - extracellular vesicle , inflammation , biomarker , microrna , methamphetamine , microvesicles , extracellular , extracellular vesicles , drug , neuroinflammation , biology , immunology , medicine , neuroscience , microbiology and biotechnology , pharmacology , gene , biochemistry
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 EV‐associated 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 from MUD subjects, 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 EV‐associated 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.