Neuron
Volume 43, Issue 1, 8 July 2004, Pages 31-42
Journal home page for Neuron

Article
Conditional Deletion of TrkB but Not BDNF Prevents Epileptogenesis in the Kindling Model

https://doi.org/10.1016/j.neuron.2004.06.019Get rights and content
Under an Elsevier user license
open archive

Abstract

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.

Cited by (0)

5

These authors contributed equally to this work.