{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:04:48Z","timestamp":1773212688372,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 MH087332"],"award-info":[{"award-number":["R01 MH087332"]}]},{"name":"NIH","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}]},{"name":"NIH","award":["R01 MH105330"],"award-info":[{"award-number":["R01 MH105330"]}]},{"name":"NIH","award":["R01 DA052209"],"award-info":[{"award-number":["R01 DA052209"]}]},{"name":"NIH","award":["P50 DA026306"],"award-info":[{"award-number":["P50 DA026306"]}]},{"name":"NIH","award":["R25 MH081482"],"award-info":[{"award-number":["R25 MH081482"]}]},{"name":"TMARC Project 5","award":["R01 MH087332"],"award-info":[{"award-number":["R01 MH087332"]}]},{"name":"TMARC Project 5","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}]},{"name":"TMARC Project 5","award":["R01 MH105330"],"award-info":[{"award-number":["R01 MH105330"]}]},{"name":"TMARC Project 5","award":["R01 DA052209"],"award-info":[{"award-number":["R01 DA052209"]}]},{"name":"TMARC Project 5","award":["P50 DA026306"],"award-info":[{"award-number":["P50 DA026306"]}]},{"name":"TMARC Project 5","award":["R25 MH081482"],"award-info":[{"award-number":["R25 MH081482"]}]},{"name":"IRFN Fellowship","award":["R01 MH087332"],"award-info":[{"award-number":["R01 MH087332"]}]},{"name":"IRFN Fellowship","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}]},{"name":"IRFN Fellowship","award":["R01 MH105330"],"award-info":[{"award-number":["R01 MH105330"]}]},{"name":"IRFN Fellowship","award":["R01 DA052209"],"award-info":[{"award-number":["R01 DA052209"]}]},{"name":"IRFN Fellowship","award":["P50 DA026306"],"award-info":[{"award-number":["P50 DA026306"]}]},{"name":"IRFN Fellowship","award":["R25 MH081482"],"award-info":[{"award-number":["R25 MH081482"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Methamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model of neuroHIV with inducible expression of HIV-1 transactivator of transcription (Tat). Seven months after transient Tat induction and five months after METH exposure ended, we detected behavioral changes in the Barnes maze (BM) spatial memory task in the Tat and METH groups but not the combined Tat + METH group. The novel object recognition (NOR) task revealed that Tat extinguished discrimination in female animals with and without METH, although METH alone slightly improved NOR. In contrast, in males, Tat, METH, and Tat + METH all compromised NOR. Neuropathological examination detected sex-dependent and brain region-specific changes of pre-synaptic terminals, neurites, and activation of astrocytes and microglia. RNA-sequencing and quantitative reverse transcription polymerase chain reaction indicated that METH and Tat significantly altered gene expression, including factors linked to Alzheimer\u2019s disease-like NCI. In summary, chronic low-dose METH exerts long-term effects on behavioral function, neuropathology, and mRNA expression, and modulates the effects of Tat, suggesting sex-dependent and -independent mechanisms may converge in HIV brain injury and NCI.<\/jats:p>","DOI":"10.3390\/v17030361","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T07:37:17Z","timestamp":1740987437000},"page":"361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic, Low-Dose Methamphetamine Reveals Sexual Dimorphism of Memory Performance, Histopathology, and Gene Expression Affected by HIV-1 Tat Protein in a Transgenic Model of NeuroHIV"],"prefix":"10.3390","volume":"17","author":[{"given":"Indira S.","family":"Harahap-Carrillo","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside (UCR), Riverside, CA 92521, 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0722-2509","authenticated-orcid":false,"given":"Daniel","family":"Ojeda-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside (UCR), Riverside, CA 92521, USA"},{"name":"Center for Infectious and Inflammatory Disease, Sanford Burnham Prebys Medical Discovery Institute (SBP), La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria E.","family":"Thaney","sequence":"additional","affiliation":[{"name":"Center for Infectious and Inflammatory Disease, Sanford Burnham Prebys Medical Discovery Institute (SBP), La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4661-8378","authenticated-orcid":false,"given":"Ana B.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Translational Methamphetamine AIDS Research Center (TMARC), Department of Psychiatry, University of California, San Diego (UCSD), San Diego, CA 92093, USA"},{"name":"Center for Infectious and Inflammatory Disease, Sanford Burnham Prebys Medical Discovery Institute (SBP), La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Godzik","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside (UCR), Riverside, CA 92521, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4044-8884","authenticated-orcid":false,"given":"Amanda J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute (TSRI), Animal Models Core, La Jolla, CA 92037, 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