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Over the last decade there has been a dramatic increase in deaths related to opioid overdose. While opioid abuse has been shown to result in increased neuroinflammation, mechanism(s) underlying this process, remain less understood. In recent years, microRNAs have emerged as key mediators of gene expression regulating both paracrine signaling and cellular crosstalk. MiRNAs constitute the extracellular vesicle (EV) cargo and can shuttle from the donor to the recipient cells. Exposure of human primary astrocytes to morphine resulted in induction and release of miR\u2010138 in the EVs isolated from conditioned media of cultured astrocytes. Released EVs were, in turn, taken up by the microglia, leading to activation of these latter cells. Interestingly, activation of microglia involved binding of the GUUGUGU motif of miR138 to the endosomal toll like receptor (TLR)7, leading, in turn, to cellular activation. These findings were further corroborated in vivo in wildtype mice wherein morphine administration resulted in increased microglial activation in the thalamus. In TLR7\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice on the other hand, morphine failed to induce microglial activation. These findings have ramifications for the development of EV\u2010loaded anti\u2010miRNAs as therapeutics for alleviating neuroinflammation in opioids abusers.\n                  <\/jats:p>","DOI":"10.1002\/jev2.12027","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T10:44:06Z","timestamp":1606992246000},"source":"Crossref","is-referenced-by-count":55,"title":["Morphine\u2010mediated release of miR\u2010138 in astrocyte\u2010derived extracellular vesicles promotes microglial activation"],"prefix":"10.1002","volume":"10","author":[{"given":"Ke","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoku","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake","family":"Dallon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney","family":"Villarreal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Buch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2011.1827"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00428-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"issue":"2","key":"e_1_2_7_7_1","first-page":"713","article-title":"Exosomal lncRNAATB activates astrocytes that promote glioma cell invasion","volume":"54","author":"Bian E. 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