Microglia in human immunodeficiency virus-associated neurodegeneration.
Infection with the human immunodeficiency virus (HIV) is associated with a syndrome of cognitive and motor abnormalities that may develop in the absence of opportunistic infections. Neurons are not productively infected by HIV. Thus, one hypothesis to explain the pathophysiology of HIV-associated dementia (HAD) suggests that signals released from other infected cell types in the CNS secondarily lead to neuronal injury. Microglia are the predominant resident CNS cell type productively infected by HIV-1. Neurologic dysfunction in HAD appears to be a consequence of microglial infection and activation. Several neurotoxic immunomodulatory factors are released from infected and activated microglia, leading to altered neuronal function, synaptic and dendritic degeneration, and eventual neuronal apoptosis. This review summarizes findings from clinical/pathological studies, animal models, and in vitro models of HAD. Most of these studies support the hypothesis that altered microglial physiology is the nidus for a cascade of events leading to neuronal dysfunction and death. Several molecular mediators of neuronal injury in HAD that emanate from microglia have been identified, and strategies for altering the impact of these neurotoxins are discussed.
Garden
Gwenn A
GA
Department of Neurology, University of Washington, Seattle, Washington.
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000633:toxicity; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000096:biosynthesis / Q000633:toxicity; D015488:HIV Antigens / Q000276:immunology / Q000633:toxicity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000633:toxicity
D018925:Chemokines; D018846:Excitatory Amino Acids; D015488:HIV Antigens; D014759:Viral Envelope Proteins