AMPA KAINATE RECEPTORS MODULATE THE SURVIVAL IN-VITRO OF EMBRYONIC BRAIN-STEM CELLS/

This study aimed at analyzing the involvement of alpha-amino--hydroxy- 5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) receptors in the survival of cultured rat embryonic brainstem cells, dissociated o n embryonic day 14. The cell number was estimated after pharmacologica l manipulation of the receptors by exposure to agonists or antagonists . The developmental stage at the moment of drug application was critic al for cell survival. We observed after 8 days in vitro a much stronge r decrease in the number of gamma-enolase-positive cells when the cult ures were treated for 3 days with the antagonist 6,7-dinitroquinoxalin e-2,3-dione (DNQX) starting on the day of plating than when DNQX was a dded after 5 days in vitro. Conversely, exposure to the agonists hydro xy-5-tri-fluoromethyl-4-isoxazolyl)-propionic acid (T-AMPA) or kainate for 3 days significantly reduced cell survival only when the treatmen t was initiated after 5 days in vitro. Survival of S-100-positive cell s was not affected after exposure to either agonists or antagonists. N either agonist nor antagonist treatment modified cell proliferation, a s assessed by 5-bromo-2'-deoxyuridine (BrdU) staining, suggesting that the decrease in the number of gamma-enolase-positive cells is essenti ally due to cell death. If some of the processes we observed in vitro correspond to analogous events in vivo, then exposure to excitatory am ino acid receptor agonists or antagonists at critical stages of embryo genesis may alter the development of the central nervous system. (C) 1 997 ISDN.