Serum Exosomal MicroRNA-137 Predicts Repeated Psychostimulant Exposure after Prolonged Abstinence = Serum Exosomal MicroRNA-137 Predicts Repeated Psychostimulant Exposure after Prolonged Abstinence

다국어 초록 (Multilingual Abstract)

Background: Repeated exposure to psychostimulant results in various chronic alterations after a period of prolonged abstinence. However, method for determining the repeated exposure to psychostimulant after long-term abstinence (months to years) has been absent. MicroRNAs (miRNAs) can cross blood-brain barrier, either in free or exosome-enwrapped form, and a significant amount of exosomal miRNAs circulates within blood serum. Considering that striatum is an epicenter of long-term changes underlying addiction, the striatum-derived miRNAs in bloodstream may prove to be a suitable biomarker for detecting repeated psychostimulant exposure after prolonged abstinence. Methods and Results: Based on the miRNA expression profiling studies, we selected two candidate miRNAs (miR-137 and -132) that are evolutionarily conserved, brain-enriched and specific to cocaine addiction in terms of striatal expression changes and role in neuroplasticity. Between the candidate miRNAs, we demonstrate that miR-137 is concordantly diminished in striatum and serum exosome of mice after weeks of abstinence from repeated cocaine exposure, and that the striatal and serum exosomal miR-137 levels display strong correlation during the prolonged abstinence. Additionally, we show that the reduction in human serum exosomal miR-137 can effectively distinguish methamphetamine-addicted patients after several months to years of abstinence. Finally, we provide evidences that RNAs of striatal origin can be found in serum exosome, suggesting that the circulating brain-enriched miR-137 may be directly derived from striatum. Conclusions: Overall, our study indicates serum exosomal miR-137 as a potentially non-invasive, sensitive and reliable biomarker reflecting long-term striatal changes after the prolonged abstinence from repeated psychostimulant exposure. Acknowledgement: This research was funded by the Korea Institute of Science and Technology Intramural Funding (No. 2E25210) and Center for Women In Science, Engineering, and Technology (WISET) grant funded by the Korea government (MEST) (No. 2N38873).