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To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a\/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M<jats:sub>3<\/jats:sub>R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a<jats:sup>+<\/jats:sup>O4<jats:sup>+<\/jats:sup>cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M<jats:sub>3<\/jats:sub>R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinated<jats:italic>shiverer\/rag2<\/jats:italic>brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors.<\/jats:p>","DOI":"10.1523\/jneurosci.3510-14.2015","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T06:43:23Z","timestamp":1424933003000},"page":"3676-3688","source":"Crossref","is-referenced-by-count":80,"title":["Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair"],"prefix":"10.1523","volume":"35","author":[{"given":"Kavitha","family":"Abiraman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyog U.","family":"Pol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie 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