Serum deprivation-induced apoptosis in cultured hippocampi is prevented by kainate.
Serum deprivation of hippocampal organotypic cultures induced cell death within 6 h in dentate gyrus granule cells and hilar interneurons whereas neurons from other hippocampal regions were spared. Dying neurons exhibited condensed chromatin in the nuclei, as revealed by cresyl violet, Hoescht staining, and electron microscopy. Cell death was abolished by cycloheximide. KA, an agonist of AMPA/KA receptors that induces depolarization, also prevented neuronal death. This effect was antagonized by the AMPA/KA receptor antagonist DNQX, but not by APV, an antagonist of NMDA receptors. PTX, a GABA(A) receptor antagonist, reduced neuronal death by 50% after serum withdrawal. These data indicate that protein synthesis-dependent programmed cell death (PCD) occurs in the dentate gyrus upon trophic support withdrawal and suggest that neuronal activity contributes to cellular homeostasis.
Rivera
S
S
Université René Descartes, Paris V, INSERM Unité 29, France.
Guillot
S
S
Agassandian
C
C
Ben Ari
Y
Y
Khrestchatisky
M
M
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D003513:Cycloheximide / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016895:Culture Media, Serum-Free; D003513:Cycloheximide; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007608:Kainic Acid; D010852:Picrotoxin; D011500:Protein Synthesis Inhibitors; D011810:Quinoxalines; C056723:FG 9041