AMPA/kainate receptors modulate the survival in vitro of embryonic brainstem cells.
This study aimed at analyzing the involvement of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) receptors in the survival of cultured rat embryonic brainstem cells, dissociated on embryonic day 14. The cell number was estimated after pharmacological manipulation of the receptors by exposure to agonists or antagonists. The developmental stage at the moment of drug application was critical for cell survival. We observed after 8 days in vitro a much stronger decrease in the number of gamma-enolase-positive cells when the cultures were treated for 3 days with the antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) starting on the day of plating than when DNQX was added after 5 days in vitro. Conversely, exposure to the agonists (RS)-2-amino-3-(3-hydroxy-5-tri-fluoromethyl-4-isoxazolyl)-propion ic acid (T-AMPA) or kainate for 3 days significantly reduced cell survival only when the treatment was initiated after 5 days in vitro. Survival of S-100-positive cells was not affected after exposure to either agonists or antagonists. Neither agonist nor antagonist treatment modified cell proliferation, as assessed by 5-bromo-2'-deoxyuridine (BrdU) staining, suggesting that the decrease in the number of gamma-enolase-positive cells is essentially due to cell death. If some of the processes we observed in vitro correspond to analogous events in vivo, then exposure to excitatory amino acid receptor agonists or antagonists at critical stages of embryogenesis may alter the development of the central nervous system.
Bardoul
M
M
INSERM U336 and EPHE Neurobiologie Cellulaire Quantitative, University of Montpellier II, France.
Drian
M J
MJ
König
N
N
D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D001973:Bromodeoxyuridine / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D009418:S100 Proteins / Q000032:analysis
D001973:Bromodeoxyuridine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010751:Phosphopyruvate Hydratase; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D009418:S100 Proteins