Kainate-induced apoptotic cell death in hippocampal neurons.
We have examined the role apoptosis plays in epileptic brain damage using intra-amygdaloid injection of kainate. With the silver staining technique of Gallyas, argyrophylic (dying) neurons were observed, a few hours after the injection, in the amygdala and in the vulnerable pyramidal neurons of the hippocampal CA3 region. In both areas, cell death has apoptotic features, including: (i) nuclear chromatin condensation and marginalization with light and electron microscopy; (ii) DNA fragmentation with a typical ladder pattern on agarose gel electrophoresis; (iii) positive nuclear labelling with a selective in situ DNA fragmentation staining method. Combined in situ DNA labelling and silver staining showed that the DNA fragmentation occurred in dying neurons. CA1 or granule cells which do not degenerate following intra-amygdaloid injection of kainate were not stained with the in situ DNA labelling or the argyrophylic technique. Administration of diazepam blocked the kainate-induced seizures and prevented DNA fragmentation in CA3 but not in the amygdala. Therefore, apoptosis contributes to the local and distant damage induced by kainate.
Pollard
H
H
INSERM U 29, Laboratoire de Neurobiologie et Physiopathologie du Développement, Hopital de Port Royal, Paris, France.
Charriaut-Marlangue
C
C
Cantagrel
S
S
Represa
A
A
Robain
O
O
Moreau
J
J
Ben-Ari
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D003975:Diazepam / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects*; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016622:Silver Staining
D004247:DNA; D003975:Diazepam; D007608:Kainic Acid