Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation in NT-3 mutant mice

Experimental Neurology
E ElmérO Lindvall

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....Continue Reading

References

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Citations

Jul 22, 2008·Epilepsia·Hal BlumenfeldStephen G Waxman
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·A NanobashviliZ Kokaia
Oct 27, 2009·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Tina MeleDamijana Mojca Juric
Oct 25, 2011·Brain Research·Rashmi M RisbudBrenda E Porter
Jun 15, 2004·Progress in Neurobiology·Kiyoshi MorimotoRonald J Racine
Oct 24, 2006·Trends in Pharmacological Sciences·Michele SimonatoMerab Kokaia
Oct 8, 2013·Brain Research·Meng-Meng LiLan Tan
Sep 18, 2012·Epilepsy Research·A Soren LeonardJames O McNamara
Jul 18, 2002·Epilepsia·Joo-Yong KimChun-Kee Chung

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