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Human imaging studies have revealed significant white matter (WM) abnormalities linked to cognitive impairment in children with FASD; however, the underlying mechanisms remain unknown. Here, we evaluated both the acute and long\u2010term impacts of alcohol exposure on oligodendrocyte number and WM integrity in a third trimester\u2010equivalent mouse model of FASD, in which mouse pups were exposed to alcohol during the first 2 weeks of postnatal development. Our results demonstrate a 58% decrease in the number of mature oligodendrocytes (OLs) and a 75% decrease in the number of proliferating oligodendrocyte progenitor cells (OPCs) within the corpus callosum of alcohol\u2010exposed mice at postnatal day 16 (P16). Interestingly, neither mature OLs nor OPCs derived from the postnatal subventricular zone (SVZ) were numerically affected by alcohol exposure, indicating heterogeneity in susceptibility based on OL ontogenetic origin. Although mature OL and proliferating OPC numbers recovered by postnatal day 50 (P50), abnormalities in myelin protein expression and microstructure within the corpus callosum of alcohol\u2010exposed subjects persisted, as assessed by western immunoblotting of myelin basic protein (MBP; decreased expression) and MRI diffusion tensor imaging (DTI; decreased fractional anisotropy). These results indicate that third trimester\u2010equivalent alcohol exposure leads to an acute, albeit recoverable, decrease in OL lineage cell numbers, accompanied by enduring WM injury. Additionally, our finding of heterogeneity in alcohol susceptibility based on the developmental origin of OLs may have therapeutic implications in FASD and other disorders of WM development.<\/jats:p>","DOI":"10.1002\/glia.23164","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T08:48:24Z","timestamp":1495097304000},"page":"1317-1332","source":"Crossref","is-referenced-by-count":62,"title":["Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-7968","authenticated-orcid":false,"given":"Jessie","family":"Newville","sequence":"first","affiliation":[{"name":"Department of Neurosciences University of New Mexico Health Sciences Center Albuquerque New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos 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