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

Xiao Ping He, Robert Kotloski, Serge Nef, Bryan W. Luikart, Luis F. Parada, James O. McNamara

Research output: Contribution to journalArticle

223 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalNeuron
Volume43
Issue number1
DOIs
StatePublished - Jul 8 2004

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model'. Together they form a unique fingerprint.

  • Cite this

    He, X. P., Kotloski, R., Nef, S., Luikart, B. W., Parada, L. F., & McNamara, J. O. (2004). Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron, 43(1), 31-42. https://doi.org/10.1016/j.neuron.2004.06.019