TGF-BETA-1 PREVENTS GP120-INDUCED IMPAIRMENT OF CA2-NEURONS FROM APOPTOTIC DEATH( HOMEOSTASIS AND RESCUES CORTICAL)

HIV-1 infection frequently induces neuronal death responsible for the development of neurological deficits associated with AIDS. Several rep orts suggest that gp120, the HIV-1 envelope glycoprotein, is the main candidate as mediator of the HIV-l-dependent neurotoxicity. Here we re port the effect of gp120 on the survival of cortical neurons in vitro and the possible mechanisms whereby it occurs. Mature cortical neurons , cultured on a feeder layer of astrocytes, were treated with gp120 in a defined culture medium in absence of serum. The treatment with gp12 0 induced time-dependent neuronal damage displaying apoptotic features , as revealed by in situ labelling of DNA fragmentation. TGF-beta 1, a cytokine that has been previously shown to exert neuroprotective effe cts, prevented the cell death induced by exposure of cortical neurons to gp120. The prolonged treatment with gp120 also increased neuronal [ Ca2+](i), while the coincubation with TGF-beta 1 completely prevented the impairment of neuronal Ca2+ homeostasis. These data, taken togethe r, demonstrate that gp120 induces apoptosis in cortical neurons, an ef fect that can be related to the impairment of Ca2+ homeostasis, and th at TGF-beta 1 pretreatment reverts both the neuronal death and the alt erations in neuronal [Ca2+](i). (C) 1997 Wiley-Liss, Inc.