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Using \u03b17 nAChR knockout mice, we showed that \u03b17 nAChR knockout eliminated the protective effects of PNU-125096 on iTat mice. In addition, we showed that inhibition of p38 phosphorylation by SB239063, a p38 MAPK-specific inhibitor exacerbated Tat neurotoxicity in iTat mice. Last, we used primary mouse cortical individual cultures and neuron-astrocytes co-cultures and in vivo staining of iTat mouse brain tissues and showed that glial activation was directly involved in the interplay among Tat neurotoxicity, \u03b17 nAChR activation and the p38 MAPK signalling pathway.<\/jats:p><jats:p>Taken together, these findings demonstrated for the first time that \u03b17 nAChR activation led to protection against HAND and suggested that \u03b17 nAChR modulator PNU-125096 holds significant promise for development of therapeutics for HAND.<\/jats:p>","DOI":"10.1093\/brain\/awab251","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T19:20:30Z","timestamp":1625080830000},"page":"3355-3370","source":"Crossref","is-referenced-by-count":24,"title":["Activation of \u03b17 nicotinic acetylcholine receptor ameliorates HIV-associated neurology and neuropathology"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8080-0280","authenticated-orcid":false,"given":"Xiaojie","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA"},{"name":"Center for Cancer Cell Biology, Immunology and Infection, Rosalind Franklin University, North Chicago, IL 60064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-6302","authenticated-orcid":false,"given":"Kelly","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA"},{"name":"Center for Cancer Cell Biology, Immunology and Infection, Rosalind Franklin University, North Chicago, IL 60064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Uteshev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Graduate School of Biomedical Sciences of University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny J","family":"He","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA"},{"name":"Center for Cancer Cell Biology, Immunology and Infection, Rosalind Franklin University, North Chicago, IL 60064, USA"},{"name":"School of Graduate and Postdoctoral Studies, Rosalind Franklin University, North Chicago, IL 60064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"2021121702004984300_awab251-B1","first-page":"S69","article-title":"The incubation period of AIDS","volume":"11 (Suppl A","author":"Munoz","year":"1997","journal-title":"AIDS"},{"key":"2021121702004984300_awab251-B2","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/S0140-6736(00)02069-9","article-title":"Survival after introduction of HAART in people with known duration of HIV-1 infection. 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