GP120 AS AN ETIOLOGIC AGENT FOR NEUROAIDS - NEUROTOXICITY AND MODEL SYSTEMS

The search for an agent that can mediate the symptoms of NeuroAIDS has been directed at gp120, the major envelope protein from HIV. The toxi city associated with gp120 was examined asa model and predictor of the neuropathological and neuropsychiatric manifestations of AIDS. Studie s of the neurotoxic effects of purified gp120 on neurons from the rode nt CNS cell cultures indicated the following: potent and selective kil ling of subpopulations of hippocampal neurons; varying potency of gp12 0s obtained from various HIV isolates; complete and potent protection from gp120 killing action after treatment with peptides related to vas oactive intestinal peptide; and obligatory presence of glia for gp120- related toxicity. Investigations of gp120 treatment of rodents reveale d: cortical neurodystrophy with reduced arborizations and swollen proc esses; delays in developmental behaviors involving motor skills; pepti de T prevention or attenuation of the morphological and behavioral def icits/delays produced by administration of gp120; and impairment of le arning in the Morris swim maze. In addition, studies of subcutaneously administered, radiolabeled gp120 in neonatal animals demonstrated the presence of toxic fragments of gp120 in the developing brain. With th e use of model test systems of nonhuman derived cell cultures and neon atal rats, we have captured and predicted a number of the morphologica l and behavioral deficits associated with AIDS. These multidisciplinar y studies of the actions of gp120 and associated fragments in rodents and rodent cells predict that the loss of cognitive and neurological f unction in patients with AIDS are attributed in part to interference o f critical brain functions by the envelope protein, gp120.