Human immunodeficiency virus–associated neurocognitive disorder

Nath, Avindra

doi:10.1111/j.1749-6632.2009.05277.x

Cited by 76 publications

(79 citation statements)

References 69 publications

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“…The combined effects of methamphetamine and HIV on cognitive function have been difficult to investigate in clinical populations because of polydrug abuse (i.e., the concomitant abuse of other drugs in addition to methamphetamine) and noncompliance with medications in drug-abusing subjects (Nath, 2010). The rate of global neurocognitive impairment tends to be greater in HIV-infected methamphetamine-dependent patients than in individuals who are either HIV-infected or methamphetamine-dependent only (Rippeth et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

Woods¹,

Carr²,

Letendre³

et al. 2015

European Neuropsychopharmacology

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Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult.

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Section: Introductionmentioning

confidence: 99%

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

Woods¹,

Carr²,

Letendre³

et al. 2015

European Neuropsychopharmacology

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“…The neuropathology of HAND is complex, although consistent findings associated with severe forms include elevation of inflammatory cytokines (11), high levels of excitotoxins (12), neuronal loss (13), and decreased synaptic density (14)(15)(16)(17). HAND is both accelerated and complicated by the frequent comorbidity of illicit drug abuse, primarily intravenous opiate abuse (18)(19)(20); compared with non-drug-abusing HIV patients, drugabusing HIV patients exhibited increased HIV encephalitis frequency (21), enhanced microglia activation (22), promotion of giant cell formation (23), and increased blood-brain barrier disruption (21).…”

Section: Introductionmentioning

confidence: 99%

Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction

Pitcher¹,

Abt²,

Myers³

et al. 2014

J. Clin. Invest.

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Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that μ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS.

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“…For example, HIV-infected patients using methamphetamine (METH) show more neurocognitive deficits, compared to those not using METH (Nath 2010). These findings are not surprising, as illicit drugs, such as morphine and methamphetamine, alter the BBB permeability through direct damage to the BMVECs (Ramirez, Potula et al 2009).…”

Section: Drugs Of Abusementioning

confidence: 76%