Excitotoxicity and dopaminergic dysfunction in the acquired immunodeficiency syndrome dementia complex. Therapeutic implications
K. D. Kieburtz, L. G. Epstein, H. A. Gelbard and J. T. Greenamyre
Department of Neurology, University of Rochester Medical Center, NY 14642.
Human immunodeficiency virus infection is frequently complicated by a
syndrome of central nervous system dysfunction known as the acquired
immunodeficiency syndrome dementia complex (ADC). The ADC is characterized
by abnormalities in cognition, motor performance, and behavior, and it
produces serious morbidity in a significant number of patients with
acquired immunodeficiency syndrome. The pathogenesis of ADC is unclear, but
appears to be caused by the human immunodeficiency virus itself, rather
than by a secondary opportunistic process. Herein, we review the data
regarding the pathogenesis of ADC and hypothesize a mechanism involving
excitotoxicity and dopaminergic dysfunction. N-methyl-D-aspartate receptor
antagonists may be of therapeutic benefit, as these agents may both limit
glutamate-mediated neuronal dysfunction and improve dopaminergic neuronal
function.
