Overexpression of bcl-2, bcl-xL or hsp70 in murine cortical astrocytes reduces injury of co-cultured neurons

Astrocytes perform many functions that protect neurons during-stress, including transmitter uptake, metabolic support, and protection from oxidative stress. We asked whether astrocytes overexpressing either the anti-apoptotic genes bcl-2, or bcl-x(L), or the inducible heat shock protein hsp70, could better protect neurons grown with them in coculture than normal astrocytes or astrocytes expressing beta-galactosidase. Retroviral vectors were used to express these genes; in primary astrocyte cultures. After antibiotic selection to eliminate untransformed astrocytes, neurons were plated on top of the astrocytes, Overexpression of any of the three genes in astrocytes reduced neuronal injury induced by combined oxygen-glucose deprivation, or glucose deprivation. Hsp70 overexpression reduced glutamate toxicity. As none of the genes studied is thought to be secreted, the likeliest explanation for the protection observed is improved astrocyte function. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.