| | |  | | | | Record from Web of Science® | | | | | | |
| Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model |
|
|
| Author(s): He XP, Kotloski R, Nef S, Luikart BW, Parada LF, McNamara JO |
| Source: NEURON Volume: 43 Issue: 1 Pages: 31-42 Published: JUL 8 2004 |
| Times Cited: 60 References: 52 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: McNamara, JO (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA |
Addresses:
1. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
2. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA
3. Duke Univ, Med Ctr, Dept Pharmacol & Mol Canc Biol, Durham, NC 27710 USA
4. Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75390 USA
5. Univ Texas, SW Med Ctr, Kent Waldrep Fdn Ctr Basic Neurosci Res Nerve Gro, Dallas, TX 75390 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Neurosciences |
| IDS Number: 836IT |
| ISSN: 0896-6273 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |