Detection of microRNA-137 expression as a potential screening marker for psychostimulant use

Detection of microRNA-137 expression as a potential screening marker for psychostimulant use
microRNA; exosome; cocaine; striatum; biomarker
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The measurement of circulating microRNAs (miRNAs) has been the latest effort to identify novel biomarkers in preclinical safety. Significant amount of miRNAs circulate in plasma or serum either freely or contained in exosomes. Exosomes are small (40~100 nm) vesicles that originated within multi-vesicular bodies and are secreted extracellularly. We examined whether exosomal miRNAs in the blood might reflect the changes in the brain by repeated cocaine exposure to mice. Mice were treated with saline or cocaine intraperitoneally, and brains and serum exosome were collected at different time points after the final injection. Changes of miRNA in brain and exosome were analyzed by qRT-PCR. We used lenti-WPRE (Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element) fragment, which does not exist in physiological conditions of mammals, to determine whether exosomal miRNAs in serum originated from brain tissue. Finally, we verified characterization and stability of exosome. We observed that miR-137 notably decreased in dorsal striatum (dST) and in serum exosome at 7 days and 14 days after the last cocaine exposure of the repeatedly injected group. In addition, there was robust correlation between changes of miR-137 in dST and in serum exosome. WPRE was detected in serum exosomes, which peaked at 6 hours whereas WPRE in the striatum peaked at 2 hours. We confirmed that the exosomal miRNAs including miR-137 are stable in extreme temperatures and chemical treatments compared to the non-exosomal miRNAs in serum. Our data suggest that serum exosomal miR-137 could reflect the response of the striatum to the cocaine and it may be useful for development of sensitive biomarker for psychostimulant abuse, including cocaine.
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