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Immature oligodendrocytes (OL<\/jats:styled-content>s) are quite sensitive to toxic increases in [Ca2+<\/jats:sup>]i<\/jats:sub> caused by exposure to HIV<\/jats:styled-content>\u20101 Tat (transactivator of transcription, a protein essential for HIV<\/jats:styled-content> replication and gene expression), but sensitivity to Tat\u2010induced [Ca2+<\/jats:sup>]i<\/jats:sub> is reduced in mature OL<\/jats:styled-content>s. Tat exposure also increased the activity of Ca2+<\/jats:sup>\/calmodulin\u2010dependent kinase II<\/jats:styled-content>\u03b2 (CaMKII<\/jats:styled-content>\u03b2), the major isoform of CaMKII<\/jats:styled-content> expressed by OL<\/jats:styled-content>s, in both immature and mature OL<\/jats:styled-content>s. Since CaMKII<\/jats:styled-content>\u03b2 is reported to interact with glycogen synthase kinase 3\u03b2 (GSK<\/jats:styled-content>3\u03b2), and GSK<\/jats:styled-content>3\u03b2 activity is implicated in OL<\/jats:styled-content> apoptosis as well as HIV<\/jats:styled-content> neuropathology, we hypothesized that disparate effects of Tat on OL<\/jats:styled-content> viability with maturity might be because of an altered balance of CaMKII<\/jats:styled-content>\u03b2\u2013GSK<\/jats:styled-content>3\u03b2 activities. Tat expression in\u00a0vivo<\/jats:italic> led to increased CaMKII<\/jats:styled-content>\u03b2 and GSK<\/jats:styled-content>3\u03b2 activity in multiple brain regions in transgenic mice. In vitro,<\/jats:italic> immature murine OL<\/jats:styled-content>s expressed higher levels of GSK<\/jats:styled-content>3\u03b2, but much lower levels of CaMKII<\/jats:styled-content>\u03b2, than did mature OL<\/jats:styled-content>s. Exogenous Tat up\u2010regulated GSK<\/jats:styled-content>3\u03b2 activity in immature, but not mature, OL<\/jats:styled-content>s. Tat\u2010induced death of immature OL<\/jats:styled-content>s was rescued by the GSK<\/jats:styled-content>3\u03b2 inhibitors valproic acid or SB<\/jats:styled-content>415286, supporting involvement of GSK<\/jats:styled-content>3\u03b2 signaling. Pharmacologically inhibiting CaMKII<\/jats:styled-content>\u03b2 increased GSK<\/jats:styled-content>3\u03b2 activity in Tat\u2010treated OL<\/jats:styled-content>s, and genetically knocking down CaMKII<\/jats:styled-content>\u03b2 promoted death in mature OL<\/jats:styled-content> cultures treated with Tat. Together, these results suggest that the effects of Tat on OL<\/jats:styled-content> viability are dependent on CaMKII<\/jats:styled-content>\u03b2\u2013GSK<\/jats:styled-content>3\u03b2 interactions, and that increasing CaMKII<\/jats:styled-content>\u03b2 activity is a potential approach for limiting OL<\/jats:styled-content>\/myelin injury with HIV<\/jats:styled-content> infection.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14668","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T19:16:17Z","timestamp":1548357377000},"page":"98-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of HIV<\/scp>\u20101 Tat on oligodendrocyte viability are mediated by CaMKII<\/scp>\u03b2\u2013GSK<\/scp>3\u03b2 interactions"],"prefix":"10.1111","volume":"149","author":[{"given":"Shiping","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University School of Medicine Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce M.","family":"Balinang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University School of Medicine Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University School of Medicine Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt F.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University School of Medicine Richmond 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