HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse.
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.
Hauser
Kurt F
KF
Department of Anatomy and Neurobiology, University of Kentucky College of medicine, Lexington, KY 40536-0298, USA.
El-Hage
Nazira
N
Stiene-Martin
Anne
A
Maragos
William F
WF
Nath
Avindra
A
Persidsky
Yuri
Y
Volsky
David J
DJ
Knapp
Pamela E
PE
D015526:AIDS Dementia Complex / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D015984:Causality; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D011619:Psychotropic Drugs / Q000009:adverse effects; D019966:Substance-Related Disorders / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
D011619:Psychotropic Drugs