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Cuprizone induced demyelination is the result of non\u2010immune mediated apoptosis of oligodendrocytes (OL) and represents a model of oligodendrogliapathy (Simmons, Pierson, Lee, &amp; Goverman, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#glia23453-bib-0042\"\/>). Glycogen Synthase Kinase (GSK) 3b has been shown to be pro\u2010apoptotic for cells other than OL. Here, we sought to investigate whether GSK3b plays a role in cuprizone\u2010induced apoptosis of OL by using a novel inducible conditional knockout (cKO) of GSK3b in mature OL. While depletion of GSK3b has no effect on survival of uninjured OL, it increases survival of mature OL exposed to cuprizone. We show that GSK3b\u2010deficient OLs are protected against caspase\u2010dependent, but not against caspase\u2010independent apoptosis. Active GSK3b is present in the nuclei of OL at peak of caspase\u2010dependent apoptosis. Significant preservation of myelinated axons is associated with GSK3b depletion and glial cell activation is markedly reduced. Collectively, the data show that GSK3b is pro\u2010apoptotic for caspase\u2010dependent cell death, likely through activation of nuclear GSK3b and its depletion promotes survival of oligodendrocytes and attenuates myelin loss.<\/jats:p>","DOI":"10.1002\/glia.23453","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T08:56:32Z","timestamp":1526374592000},"page":"1999-2012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>C<\/scp>onditional depletion of <scp>GSK<\/scp>3b protects oligodendrocytes from apoptosis and lessens demyelination in the acute cuprizone model"],"prefix":"10.1002","volume":"66","author":[{"given":"Bin","family":"Xing","sequence":"first","affiliation":[{"name":"Veterans Administration Pittsburgh, University Drive C Bldg 30 Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren E.","family":"Brink","sequence":"additional","affiliation":[{"name":"Veterans Administration Pittsburgh, University Drive C Bldg 30 Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Maers","sequence":"additional","affiliation":[{"name":"Veterans Administration Pittsburgh, University Drive C Bldg 30 Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara L.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Biologic Imaging, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Bodnar","sequence":"additional","affiliation":[{"name":"Veterans Administration Pittsburgh, University Drive C Bldg 30 Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna B.","family":"Stolz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Biologic Imaging, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-1501","authenticated-orcid":false,"given":"Franca","family":"Cambi","sequence":"additional","affiliation":[{"name":"Veterans Administration Pittsburgh, University Drive C Bldg 30 Pittsburgh Pennsylvania"},{"name":"Department of Neurology\/PIND University of Pittsburgh, 3501 5<sup>th<\/sup> Avenue Pittsburgh Pennsylvania"},{"name":"Department of Neurology University of Kentucky, 800 Rose St Lexington Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21122"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22641"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20016"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23229"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-013-9380-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.07.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203057"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.190297597"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105725200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(20000115)29:2<124::AID-GLIA5>3.0.CO;2-O"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.10.006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-98"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4261-04.2005"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401459"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200202130"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.338"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.432"},{"issue":"7","key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1242\/jcs.00384","article-title":"GSK\u20103: Tricks of the trade for a multi\u2010tasking kinase. 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