TETRODOTOXIN BLOCKS HIV COAT PROTEIN (GP120) TOXICITY IN PRIMARY NEURONAL CULTURES

HIV-1-associated cognitive/motor complex is a frequent neurological co mplication of the acquired immunodeficiency syndrome (AIDS). The patho genesis of this syndrome implicates immunopathological and toxic event s such as the production of cytokines. The HIV envelope glycoprotein g p 120 seems also to play a major role in this process. Gp 120 could pr oduce a slow neuronal death probably via the release of neurotoxic fac tors by CNS macrophages/monocytes. NMDA antagonists and Ca2+ channel b lockers in vitro have a powerfull neuroprotective effect against gp120 neurotoxicity. The purpose of the present work is to determine wether gp120-induced neurotoxicity is associated with an abnormal neuronal d epolarization induced by putative neurotoxins. We have compared in vit ro the neuroprotective effects of Tetrodotoxin a Na+ channel blocker, the Ca2+ channel blocker nifedipine and the NMDA antagonist MK-801 in primary cortical neurons taken from embryonic rat and intoxicated with gp120. We observed comparable neuroprotective effects with the 3 prec ited compounds suggesting that gp120-induced neurotoxic factors act on Na+ channels, NMDA receptors and Ca2+ channels in a cascade of cellul ar events. We confirmed that the presence of macrophages is needed to trigger a marked gp120-induced neurotoxicity. These results underline the fact that depolarization is an important component of gp120 neurot oxicity in primary neuronal cultures.