Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1111927
- author
- Bengzon, Johan LU ; Kokaia, Zaal LU ; Elmer, Eskil LU ; Nanobashvili, Avtandil LU ; Kokaia, Merab LU and Lindvall, Olle LU
- organization
- publishing date
- 1997
- 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 Academy of Sciences
- external identifiers
-
- pmid:9294228
- scopus:0030612186
- ISSN
- 1091-6490
- project
- Development of a Stem Cell Therapy for Malignant Brain Tumours
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurosurgery (013026000), Laboratory for Experimental Brain Research (013041000), Neurology, Lund (013027000)
- id
- 392e8bc9-07a2-49d4-8349-0e1097875002 (old id 1111927)
- alternative location
- http://www.pnas.org/content/94/19/10432.full
- date added to LUP
- 2016-04-01 12:28:20
- date last changed
- 2022-04-13 19:28:05
@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}}, keywords = {{kindling; epilepsy; rat; in situ DNA fragmentation; neurogenesis}}, language = {{eng}}, number = {{19}}, pages = {{10432--10437}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures}}, url = {{http://www.pnas.org/content/94/19/10432.full}}, volume = {{94}}, year = {{1997}}, }