Neurodegeneration induced by methamphetamine (METH) abuse and HIV may result in accelerated age-related brain changes leading to exacerbated cognitive deficits in the aged HIV+ population. HlV-induced neurodegeneration involves, in part, the envelope glycoprotein gpl20 and the nonstructural protein Tat. During the previous funding period we showed that gpl 20 expression induced specific deficits in reversal learning and executive function in adult mice and, when combined with METH exposure, resulted in further impairments of spatial learning. We also found that gp120 expression increased dopamine transporter levels in the nucleus accumbens and decreased calbindin levels in the hippocampus that may underlie the observed cognitive deficits. This renewal application will expand the current findings by investigating the impact of aging and METH on cognitive function in the gpl 20 and iTat transgenic mouse models that mimic the chronic and acute effects of HIV on the brain, respectively. Aged mice will be exposed to METH, tested in a battery of cognitive tests (Aim 1) and subjected to neuropathological and imaging analyses (Aim 2) using the TMARC Core resources. It is predicted that aging and METH exposure will augment cognitive deficits induced by gp120 and TAT expression and result in more pronounced neuropathology, increased inflammation and oxidative stress, compared to younger adult mice. The use of identical mouse models and METH exposure within the TMARC will facilitate the interpretation and cross comparisons of the results obtained in this project with data from other projects conducting complementary behavioral and neuropathological testing in mice. This project enhances the translational potential of TMARC by assessing in animals cognitive and neuroimaging measures that are directly analogous to those used in human studies, and cross-inform our future research directions. This project will improve our understanding of the neurobiological mechanisms underiying cognitive deficits in aging individuals with chronic HIV infection and may help identify targets for the development of therapies for neurodegeneration and cognitive deficits in HIV+ METH users.

Public Health Relevance

Aging may accelerate brain damage induced by HIV infection and METH abuse. Such brain damage results in behavioral and cognitive deficits that impair day-to-day function in humans. This project will identify neuropathological mechanisms underlying cognitive deficits associated with age, HIV and METH abuse, and thus may lead to the design of new therapeutic treatments.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California, San Diego
La Jolla
United States
Zip Code
Walker, Keenan A; Brown, Gregory G (2018) HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis. J Clin Exp Neuropsychol 40:357-376
Stecher, Melanie; Hoenigl, Martin; Eis-Hübinger, Anna Maria et al. (2018) Hotspots of Transmission Driving the Local Hiv Epidemic in the Cologne-Bonn Region, Germany. Clin Infect Dis :
Paolillo, Emily W; Obermeit, Lisa C; Tang, Bin et al. (2018) Smartphone-based ecological momentary assessment (EMA) of alcohol and cannabis use in older adults with and without HIV infection. Addict Behav 83:102-108
Thaney, Victoria E; Kaul, Marcus (2018) Type I Interferons in NeuroHIV. Viral Immunol :
Soontornniyomkij, Virawudh; Umlauf, Anya; Soontornniyomkij, Benchawanna et al. (2018) Association of antiretroviral therapy with brain aging changes among HIV-infected adults. AIDS 32:2005-2015
Thaney, Victoria E; Sanchez, Ana B; Fields, Jerel A et al. (2018) Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J Neurovirol 24:156-167
Kesby, James P; Chang, Ariel; Markou, Athina et al. (2018) Modeling human methamphetamine use patterns in mice: chronic and binge methamphetamine exposure, reward function and neurochemistry. Addict Biol 23:206-218
Hoenigl, Martin; Jain, Sonia; Moore, David et al. (2018) Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1. Emerg Infect Dis 24:
Moore, David J; Pasipanodya, Elizabeth C; Umlauf, Anya et al. (2018) Individualized texting for adherence building (iTAB) for methamphetamine users living with HIV: A pilot randomized clinical trial. Drug Alcohol Depend 189:154-160
MacDuffie, Katherine E; Brown, Gregory G; McKenna, Benjamin S et al. (2018) Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume. Neuroimage Clin 20:1044-1052

Showing the most recent 10 out of 148 publications