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We previously showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogs used for the management of pregnant addicts. Those observations suggested the involvement of the \u03bc\u2010opioid receptor (MOR) and the nociceptin\/orphanin FQ receptor (NOR). However, it remained to be determined if these receptors and their endogenous ligands could indeed control the timing of myelination under normal physiological conditions of brain development. We now found that the endogenous MOR ligand endomorphin\u20101 (EM\u20101) exerts a striking stimulatory action on cellular and morphological maturation of rat pre\u2010oligodendrocytes, but unexpectedly, these effects appear to be restricted to the cells from the female pups. Critically, this stimulation is abolished by coincubation with the endogenous NOR ligand nociceptin. Furthermore, NOR antagonist treatment of 9\u2010day\u2010old female pups results in accelerated brain myelination. Interestingly, the lack of sex\u2010dependent differences in developmental brain levels of EM\u20101 and nociceptin, or oligodendroglial expression of MOR and NOR, suggests that the observed sex\u2010specific responses may be highly dependent on important intrinsic differences between the male and female oligodendrocytes. The discovery of a significant effect of EM\u20101 and nociceptin in the developing female oligodendrocytes and brain myelination, underscores the need for further studies investigating brain sex\u2010related differences and their implications in opioid use and abuse, pain control, and susceptibility and remyelinating capacity in demyelinating disease as multiple sclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/glia.23799","type":"journal-article","created":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T12:49:15Z","timestamp":1581943755000},"page":"1513-1530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Endogenous opioid peptides and brain development: Endomorphin\u20101 and Nociceptin play a sex\u2010specific role in the control of oligodendrocyte maturation and brain myelination"],"prefix":"10.1002","volume":"68","author":[{"given":"Esraa","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin E.","family":"Paisley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan C.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Bigbee","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3619-800X","authenticated-orcid":false,"given":"Carmen","family":"Sato\u2010Bigbee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007049"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.080"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07886.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.871"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.038554"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199606)17:2<169::AID-GLIA8>3.0.CO;2-Y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10106"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(78)90258-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(98)00091-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(83)90185-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2219-05.2006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13852"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.103960"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA117.000184"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2018.1307"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.084632"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623313503518"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21253"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2017.08.007"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858408320294"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00221.2016"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20567"},{"issue":"4","key":"e_1_2_8_24_1","first-page":"210","article-title":"Comparison of HSCORE assesment of endometrial \u03b23 integrin subunit expression with digital HSCORE using computerized image analysis (ImageJ)","volume":"35","author":"Fuhrich D. 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