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Review
. 2007 Feb;100(3):567-86.
doi: 10.1111/j.1471-4159.2006.04227.x. Epub 2006 Dec 1.

HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse

Kurt F Hauser  1 , Nazira El-Hage, Anne Stiene-Martin, William F Maragos, Avindra Nath, Yuri Persidsky, David J Volsky, Pamela E Knapp
Affiliations
Review

HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse

Kurt F Hauser et al. J Neurochem. 2007 Feb.

Abstract

Neuronal dysfunction and degeneration are ultimately responsible for the neurocognitive impairment and dementia manifest in neuroAIDS. Despite overt neuronal pathology, HIV-1 does not directly infect neurons; rather, neuronal dysfunction or death is largely an indirect consequence of disrupted glial function and the cellular and viral toxins released by infected glia. A role for glia in HIV-1 neuropathogenesis is revealed in experimental and clinical studies examining substance abuse-HIV-1 interactions. Current evidence suggests that glia are direct targets of substance abuse and that glia contribute markedly to the accelerated neurodegeneration seen with substance abuse in HIV-1 infected individuals. Moreover, maladaptive neuroplastic responses to chronic drug abuse might create a latent susceptibility to CNS disorders such as HIV-1. In this review, we consider astroglial and microglial interactions and dysfunction in the pathogenesis of HIV-1 infection and examine how drug actions in glia contribute to neuroAIDS.

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Figures

Fig. 1
Fig. 1. Summary of substance abuse and HIV-1 interactions in the CNS
Opiates exacerbate the effects of HIV-1 through direct actions in µ opioid receptor (MOR)-expressing neurons, microglia and astroglia. MCP-1, IL-6, and RANTES production by astroglia are increased by heroin/morphine, which increases preexisting inflammation caused by HIV-1, increases macrophage/microglial activity and reactive oxygen species (ROS). Alcohol abuse compromises the blood brain barrier (BBB), increases viral entry, and ROS through the recruitment/enhanced turnover of macrophages within the CNS. Acute methamphetamine use increases dopamine (DA) and glutamate release and increases ROS production in DA terminals, which further compromises DA terminals damaged by methamphetamine. Cocaine blocks monoamine transporters with approximately equal affinity for the DA, serotonin (5-HT) and norepinephrine (NE) transporters disrupting signaling and contributing to local oxidative damage. Abbreviations: DA transporter (DAT); 5-HT transporter (SERT); NE transporter (NET) vesicular monoamine transporter-2 (VMAT2).
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