Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation in NT-3 mutant mice
Elmer, Eskil LU
; Kokaia, Merab
LU
; Ernfors, Patrik
; Ferencz, Istvan
LU
; Kokaia, Zaal
LU
and Lindvall, Olle
LU
(1997)
In Experimental Neurology
145(1).
p.93-103
- Abstract
- In the kindling model of epilepsy, repeated electrical stimulations lead to progressive and permanent intensification of seizure activity. We find that the development of amygdala kindling is markedly retarded in mice heterozygous for a deletion of the neurotrophin-3 (NT-3) gene (NT-3+/- mice). These mice did not reach the fully kindled state (3rd grade 5 seizure) until after 28 +/- 4 days of stimulation compared to 17 +/- 2 days in the wild-type animals. The deficit in the NT-3+/- mice reflected dampening of the progression from focal to generalized seizures. The number of stimulations required to evoke focal (grade 1 and 2) seizures did not differ between the groups, but the NT-3 mutants spent a considerably longer period of time (13 +/-... (More)
- In the kindling model of epilepsy, repeated electrical stimulations lead to progressive and permanent intensification of seizure activity. We find that the development of amygdala kindling is markedly retarded in mice heterozygous for a deletion of the neurotrophin-3 (NT-3) gene (NT-3+/- mice). These mice did not reach the fully kindled state (3rd grade 5 seizure) until after 28 +/- 4 days of stimulation compared to 17 +/- 2 days in the wild-type animals. The deficit in the NT-3+/- mice reflected dampening of the progression from focal to generalized seizures. The number of stimulations required to evoke focal (grade 1 and 2) seizures did not differ between the groups, but the NT-3 mutants spent a considerably longer period of time (13 +/- 3 days) than wild-type mice (2 +/- 1 days) in grade 2 seizures. As assessed by test stimulation 4-12 weeks after the 10th grade 5 seizure, kindling was maintained in the NT-3 mutants. In situ hybridization showed 30% reduction of basal NT-3 mRNA levels and lack of upregulation of TrkC mRNA expression at 2 h after a generalized seizure in dentate granule cells of the NT-3+/- mice, whereas the seizure-evoked increase in brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels was enhanced. These results indicate that endogenous NT-3 levels can influence the rate of epileptogenesis, and suggest a link between NT-3 and BDNF gene regulation in dentate granule cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1111482
- author
- Elmer, Eskil
LU
; Kokaia, Merab
LU
; Ernfors, Patrik
; Ferencz, Istvan
LU
; Kokaia, Zaal
LU
and Lindvall, Olle
LU
- organization
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Experimental Neurology
- volume
- 145
- issue
- 1
- pages
- 93 - 103
- publisher
- Elsevier
- external identifiers
-
- pmid:9184113
- scopus:0031148863
- pmid:9184113
- ISSN
- 0014-4886
- DOI
- 10.1006/exnr.1997.6478
- 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: Laboratory for Experimental Brain Research (013041000), Neurology, Lund (013027000)
- id
- 8173e619-e6a7-4f13-adbf-aac23c0a63ba (old id 1111482)
- date added to LUP
- 2016-04-01 12:12:53
- date last changed
- 2022-01-27 00:32:58
@article{8173e619-e6a7-4f13-adbf-aac23c0a63ba,
abstract = {{In the kindling model of epilepsy, repeated electrical stimulations lead to progressive and permanent intensification of seizure activity. We find that the development of amygdala kindling is markedly retarded in mice heterozygous for a deletion of the neurotrophin-3 (NT-3) gene (NT-3+/- mice). These mice did not reach the fully kindled state (3rd grade 5 seizure) until after 28 +/- 4 days of stimulation compared to 17 +/- 2 days in the wild-type animals. The deficit in the NT-3+/- mice reflected dampening of the progression from focal to generalized seizures. The number of stimulations required to evoke focal (grade 1 and 2) seizures did not differ between the groups, but the NT-3 mutants spent a considerably longer period of time (13 +/- 3 days) than wild-type mice (2 +/- 1 days) in grade 2 seizures. As assessed by test stimulation 4-12 weeks after the 10th grade 5 seizure, kindling was maintained in the NT-3 mutants. In situ hybridization showed 30% reduction of basal NT-3 mRNA levels and lack of upregulation of TrkC mRNA expression at 2 h after a generalized seizure in dentate granule cells of the NT-3+/- mice, whereas the seizure-evoked increase in brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels was enhanced. These results indicate that endogenous NT-3 levels can influence the rate of epileptogenesis, and suggest a link between NT-3 and BDNF gene regulation in dentate granule cells.}},
author = {{Elmer, Eskil and Kokaia, Merab and Ernfors, Patrik and Ferencz, Istvan and Kokaia, Zaal and Lindvall, Olle}},
issn = {{0014-4886}},
language = {{eng}},
number = {{1}},
pages = {{93--103}},
publisher = {{Elsevier}},
series = {{Experimental Neurology}},
title = {{Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation in NT-3 mutant mice}},
url = {{http://dx.doi.org/10.1006/exnr.1997.6478}},
doi = {{10.1006/exnr.1997.6478}},
volume = {{145}},
year = {{1997}},
}