59-4 - Role for astrocytosis in HIV-associated dementia

Abstract

HIV-1-associated dementia occurs in approximately one third of individuals infected with HIV-1, sometimes as the only presenting symptom (McArthur et al. 1994; for refinement of this number see Grant et al., this volume). It involves deficits in cognitive and higher motor functions. The dementia is linked to structural changes in neurons observed post mortem. The changes vary from dendritic dearborization to neuronal drop out (Masliah et al. 1992). Large pyramidal neurons especially vulnerable to as yet unknown pathogenic stimuli are located in the cerebral cortex. The cortex is the brain region known to control cognitive and motor functions. These functions are altered or deficient in AIDS patients. Thus, neuronal dysfunction is a likely direct cause of HIV-1-associated dementia. The precise cause and nature of neuronal dysfunction in AIDS are unknown. HIV-1-associated neuronal damage may be mediated by activation of one family of glutamate receptors (Lipton 1992). Glutamate is the major excitatory neurotransmitter in the brain. Glutamate receptor-mediated neuronal death—excitotoxicity—is implicated in the pathogenesis of several disorders affecting mental health such as Alzheimer’s dementia (Choi 1994).