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Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures

Bengzon, Johan LU ; Kokaia, Zaal LU ; Elmer, Eskil LU ; Nanobashvili, Avtandil LU ; Kokaia, Merab LU and Lindvall, Olle LU (1997) In Proceedings of the National Academy of Sciences 94(19). p.10432-10437
Abstract
Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-D-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern... (More)
Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-D-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
kindling, epilepsy, rat, in situ DNA fragmentation, neurogenesis
in
Proceedings of the National Academy of Sciences
volume
94
issue
19
pages
10432 - 10437
publisher
National Acad Sciences
external identifiers
  • pmid:9294228
  • scopus:0030612186
ISSN
1091-6490
language
English
LU publication?
yes
id
392e8bc9-07a2-49d4-8349-0e1097875002 (old id 1111927)
alternative location
http://www.pnas.org/content/94/19/10432.full
date added to LUP
2008-07-21 10:27:24
date last changed
2017-11-19 03:38:09
@article{392e8bc9-07a2-49d4-8349-0e1097875002,
  abstract     = {Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-D-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy.},
  author       = {Bengzon, Johan and Kokaia, Zaal and Elmer, Eskil and Nanobashvili, Avtandil and Kokaia, Merab and Lindvall, Olle},
  issn         = {1091-6490},
  keyword      = {kindling,epilepsy,rat,in situ DNA fragmentation,neurogenesis},
  language     = {eng},
  number       = {19},
  pages        = {10432--10437},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures},
  volume       = {94},
  year         = {1997},
}