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In this context, liver X receptors (LXRs) are the master regulators of cholesterol homeostasis in the central nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR activation leading to the transcription of target genes involved in cholesterol trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, and several ATP\u2010binding cassette transporter proteins. The disturbance of LXR signaling in the brain can lead to significant dysfunctions in cholesterol homeostasis, and disruptions in this pathway have been implicated in numerous neurological diseases including Alzheimer's disease and Huntington's disease. HIV infection of the CNS in combination with cocaine use is associated with astrocyte and neuronal energy deficit and damage. We propose that dysregulation in CNS cholesterol metabolism may be involved in the progression of HIV\u2010associated neurocognitive disorders (HAND) and in cocaine\u2010mediated neurocognitive impairments. We hypothesize that exposure of astrocytes to cocaine and the HIV protein Tat will disrupt LXR signaling. Alterations in these pathways will in turn, affect cholesterol bioavailability for neurons. Our data show that exposure of astrocytes to cocaine and HIV\u2010Tat significantly decreases LXR\u03b2 levels, downstream signaling and bioavailability of cholesterol. Taken together, these data uncover novel alterations in a bioenergetic pathway in astrocytes exposed to cocaine and the HIV protein Tat. Results from these studies point to a new pathway in the CNS that may contribute to HAND in HIV+ cocaine user individuals.<\/jats:p>","DOI":"10.1002\/glia.23291","type":"journal-article","created":{"date-parts":[[2018,1,13]],"date-time":"2018-01-13T13:44:48Z","timestamp":1515851088000},"page":"889-902","source":"Crossref","is-referenced-by-count":32,"title":["Cocaine and HIV\u20101 Tat disrupt cholesterol homeostasis in astrocytes: Implications for HIV\u2010associated neurocognitive disorders in cocaine user patients"],"prefix":"10.1002","volume":"66","author":[{"given":"Bianca","family":"Cotto","sequence":"first","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalimuthusamy","family":"Natarajaseenivasan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy","family":"Wesley","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Sayre","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5381-0531","authenticated-orcid":false,"given":"Dianne","family":"Langford","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2059"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a9565e"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000120374.59826.1b"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016212802138823"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.016"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2174\/1570162X14666160324125158","article-title":"Multiple faceted roles of cocaine in potentiation of HAND","volume":"14","author":"Cai Y.","year":"2016","journal-title":"Current HIV Research"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.03.018"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3389\/fmicb.2015.00931","article-title":"Interactive effects of cocaine on HIV infection: Implication in HIV\u2010associated neurocognitive disorder and neuroAIDS","volume":"6","author":"Dahal S.","year":"2015","journal-title":"Frontiers in Microbiology"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5473-10.2011"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s11481-016-9669-6","article-title":"HIV\u20101 Tat and cocaine impair survival of cultured primary neuronal cells via a mitochondrial pathway","volume":"11","author":"Simone F. 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