Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model.
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.
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Related Subject Headings
- Up-Regulation
- Signal Transduction
- Seizures
- Receptor, trkB
- Phosphorylation
- Neuronal Plasticity
- Neurology & Neurosurgery
- Mice, Knockout
- Mice
- Kindling, Neurologic
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Up-Regulation
- Signal Transduction
- Seizures
- Receptor, trkB
- Phosphorylation
- Neuronal Plasticity
- Neurology & Neurosurgery
- Mice, Knockout
- Mice
- Kindling, Neurologic