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Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.
Kristen A. McLaurin; Michael Harris; Victor Madormo; Steven B. Harrod; Charles F. Mactutus; Rosemarie M. Booze. HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits. Cells 2021, 10, 2158 .
AMA StyleKristen A. McLaurin, Michael Harris, Victor Madormo, Steven B. Harrod, Charles F. Mactutus, Rosemarie M. Booze. HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits. Cells. 2021; 10 (8):2158.
Chicago/Turabian StyleKristen A. McLaurin; Michael Harris; Victor Madormo; Steven B. Harrod; Charles F. Mactutus; Rosemarie M. Booze. 2021. "HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits." Cells 10, no. 8: 2158.
The persistence of HIV-1 viral reservoirs in the brain, despite treatment with combination antiretroviral therapy (cART), remains a critical roadblock for the development of a novel cure strategy for HIV-1. To enhance our understanding of viral reservoirs, two complementary studies were conducted to (1) evaluate the HIV-1 mRNA distribution pattern and major cell type expressing HIV-1 mRNA in the HIV-1 transgenic (Tg) rat, and (2) validate our findings by developing and critically testing a novel biological system to model active HIV-1 infection in the rat. First, a restricted, region-specific HIV-1 mRNA distribution pattern was observed in the HIV-1 Tg rat. Microglia were the predominant cell type expressing HIV-1 mRNA in the HIV-1 Tg rat. Second, we developed and critically tested a novel biological system to model key aspects of HIV-1 by infusing F344/N control rats with chimeric HIV (EcoHIV). In vitro, primary cultured microglia were treated with EcoHIV revealing prominent expression within 24 h of infection. In vivo, EcoHIV expression was observed seven days after stereotaxic injections. Following EcoHIV infection, microglia were the major cell type expressing HIV-1 mRNA, results that are consistent with observations in the HIV-1 Tg rat. Within eight weeks of infection, EcoHIV rats exhibited neurocognitive impairments and synaptic dysfunction, which may result from activation of the NogoA-NgR3/PirB-RhoA signaling pathway and/or neuroinflammation. Collectively, these studies enhance our understanding of HIV-1 viral reservoirs in the brain and offer a novel biological system to model HIV-associated neurocognitive disorders and associated comorbidities (i.e., drug abuse) in rats.
Hailong Li; Kristen McLaurin; Jessica Illenberger; Charles Mactutus; Rosemarie Booze. Microglial HIV-1 Expression: Role in HIV-1 Associated Neurocognitive Disorders. Viruses 2021, 13, 924 .
AMA StyleHailong Li, Kristen McLaurin, Jessica Illenberger, Charles Mactutus, Rosemarie Booze. Microglial HIV-1 Expression: Role in HIV-1 Associated Neurocognitive Disorders. Viruses. 2021; 13 (5):924.
Chicago/Turabian StyleHailong Li; Kristen McLaurin; Jessica Illenberger; Charles Mactutus; Rosemarie Booze. 2021. "Microglial HIV-1 Expression: Role in HIV-1 Associated Neurocognitive Disorders." Viruses 13, no. 5: 924.