Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

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dc.creatorZhao, Xiaojie
dc.creatorFan, Yan
dc.creatorVann, Philip H.
dc.creatorWong, Jessica M.
dc.creatorSumien, Nathalie
dc.creatorHe, Johnny J.
dc.creator.orcid0000-0002-0077-9873 (Sumien, Nathalie)
dc.date.accessioned2022-07-11T15:29:26Z
dc.date.available2022-07-11T15:29:26Z
dc.date.issued2020-02-01
dc.description.abstractHIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo. In this study, we took advantage of the doxycycline-inducible brain-specific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice. Long-term Tat expression led to poorer short-and long-term memory, lower locomotor activity and impaired coordination and balance ability, increased astrocyte activation and compromised neuronal integrity, and decreased global genomic DNA methylation. There were sex- and brain region-dependent differences in behaviors, pathologies, and epigenetic changes resulting from long-term Tat expression. All these changes are reminiscent of accelerated aging, raising the possibility that HIV Tat contributes, at least in part, to HIV infection-associated accelerated aging in HIV-infected individuals. These findings also suggest another utility of this model for HIV infection-associated accelerated aging studies.
dc.description.sponsorshipThis work was supported in part by the grants NIH/NINDS R01NS094108 and NIH/NIDA R01DA 043162 (to JJH).
dc.identifier.citationZhao, X., Fan, Y., Vann, P. H., Wong, J. M., Sumien, N., & He, J. J. (2020). Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging. Aging and disease, 11(1), 93-107. https://doi.org/10.14336/AD.2019.0323
dc.identifier.issn2152-5250
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31558
dc.identifier.volume11
dc.publisherInternational Society on Aging and Disease
dc.relation.urihttps://doi.org/10.14336/AD.2019.0323
dc.rights.holderCopyright : © 2019 Zhao et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceAging and Disease
dc.subjectDNA methylation
dc.subjectDNA methyltransferases
dc.subjectHIV-1 Tat
dc.subjectaccelerated aging
dc.titleLong-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging
dc.typeArticle
dc.type.materialtext

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