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

Publication ,  Journal Article
He, X-P; Kotloski, R; Nef, S; Luikart, BW; Parada, LF; McNamara, JO
Published in: Neuron
July 8, 2004
Published version (DOI) Link to item

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.

Duke Scholars

James O'Connell McNamara Sr.
Author James O'Connell McNamara Sr. Neurobiology

Published In

Neuron

DOI

10.1016/j.neuron.2004.06.019

ISSN

0896-6273

Publication Date

July 8, 2004

Volume

43

Issue

1

Start / End Page

31 / 42

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Seizures
  • Receptor, trkB
  • Phosphorylation
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Mice, Knockout
  • Mice
  • Kindling, Neurologic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
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
He, Xiao-Ping, Robert Kotloski, Serge Nef, Bryan W. Luikart, Luis F. Parada, and James O. McNamara. “Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model.” Neuron 43, no. 1 (July 8, 2004): 31–42. https://doi.org/10.1016/j.neuron.2004.06.019.
He X-P, Kotloski R, Nef S, Luikart BW, Parada LF, McNamara JO. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron. 2004 Jul 8;43(1):31–42.
He, Xiao-Ping, et al. “Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model.” Neuron, vol. 43, no. 1, July 2004, pp. 31–42. Pubmed, doi:10.1016/j.neuron.2004.06.019.
He X-P, Kotloski R, Nef S, Luikart BW, Parada LF, McNamara JO. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron. 2004 Jul 8;43(1):31–42.
Journal cover image

Published In

Neuron

DOI

10.1016/j.neuron.2004.06.019

ISSN

0896-6273

Publication Date

July 8, 2004

Volume

43

Issue

1

Start / End Page

31 / 42

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Seizures
  • Receptor, trkB
  • Phosphorylation
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Mice, Knockout
  • Mice
  • Kindling, Neurologic