Abstract
Chronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.e., resembling a therapeutic for children with PHIV) and across the factor of biological sex. Utilization of a series of signal detection operant tasks revealed prominent, sex-dependent neurocognitive deficits in the HIV-1 Tg rat, characterized by alterations in stimulus-reinforcement learning, the response profile, and temporal processing. Early (i.e., postnatal day 28) initiation of SE treatment precluded the development of chronic neurocognitive impairments in all (i.e., 100%) HIV-1 Tg animals, albeit not for all neurocognitive domains. Most notably, the therapeutic effects of SE are generalized across the factor of biological sex, despite the presence of endogenous hormones. Results support, therefore, the efficacy of SE as a neuroprotective therapeutic for chronic neurocognitive impairments in the post-cART era; an adjunctive therapeutic that demonstrates high efficacy in both males and females. Optimizing treatment conditions by evaluating multiple factors (i.e., age, neurocognitive domains, and biological sex) associated with PHIV and HIV-1 associated neurocognitive disorders (HAND) affords a key opportunity to improve the therapeutic efficacy of SE.
Original language | English |
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Pages (from-to) | 704-718 |
Number of pages | 15 |
Journal | Journal of NeuroVirology |
Volume | 26 |
Issue number | 5 |
DOIs | |
State | Published - Oct 1 2020 |
Bibliographical note
Publisher Copyright:© 2020, Journal of NeuroVirology, Inc.
Funding
This work was supported in part by grants from the NIH (National Institute on Drug Abuse, DA013137; National Institute of Child Health and Human Development, HD043680; National Institute of Mental Health, MH106392; National Institute of Neurological Disorders and Stroke, NS100624) and the interdisciplinary research training program supported by the University of South Carolina Behavioral-Biomedical Interface Program. Acknowledgments
Funders | Funder number |
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University of South Carolina Behavioral-Biomedical Interface Program | |
National Institutes of Health (NIH) | |
National Institute of Mental Health | MH106392 |
National Institute on Drug Abuse | DA013137 |
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | NS100624 |
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research | R01HD043680 |
Keywords
- Biological sex
- S-Equol
- Signal detection
- Stimulus-reinforcement learning
- Temporal processing
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Virology