Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model.

Published

Journal Article

Epileptogenesis is the process whereby a normal brain becomes epileptic. We hypothesized that the neurotrophin brain-derived neurotrophic factor (BDNF) activates its receptor, TrkB, in the hippocampus during epileptogenesis and that BDNF-mediated activation of TrkB is required for epileptogenesis. We tested these hypotheses in Synapsin-Cre conditional BDNF(-/-) and TrkB(-/-) mice using the kindling model. Despite marked reductions of BDNF expression, only a modest impairment of epileptogenesis and increased hippocampal TrkB activation were detected in BDNF(-/-) mice. In contrast, reductions of electrophysiological measures and no behavioral evidence of epileptogenesis were detected in TrkB(-/-) mice. Importantly, TrkB(-/-) mice exhibited behavioral endpoints of epileptogenesis, tonic-clonic seizures. Whereas TrkB can be activated, and epileptogenesis develops in BDNF(-/-) mice, the plasticity of epileptogenesis is eliminated in TrkB(-/-) mice. Its requirement for epileptogenesis in kindling implicates TrkB and downstream signaling pathways as attractive molecular targets for drugs for preventing epilepsy.

Full Text

Duke Authors

Cited Authors

  • He, X-P; Kotloski, R; Nef, S; Luikart, BW; Parada, LF; McNamara, JO

Published Date

  • July 8, 2004

Published In

Volume / Issue

  • 43 / 1

Start / End Page

  • 31 - 42

PubMed ID

  • 15233915

Pubmed Central ID

  • 15233915

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2004.06.019

Language

  • eng

Conference Location

  • United States