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

215 Citations (Scopus)

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

Fingerprint

Brain-Derived Neurotrophic Factor
trkB Receptor
Synapsins
Nerve Growth Factors
Epilepsy
Hippocampus
Seizures
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

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

Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. / He, Xiao Ping; Kotloski, Robert; Nef, Serge; Luikart, Bryan W.; Parada, Luis F.; McNamara, James O.

In: Neuron, Vol. 43, No. 1, 08.07.2004, p. 31-42.

Research output: Contribution to journalArticle

He, XP, Kotloski, R, Nef, S, Luikart, BW, Parada, LF & McNamara, JO 2004, 'Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model', Neuron, vol. 43, no. 1, pp. 31-42. https://doi.org/10.1016/j.neuron.2004.06.019
He, Xiao Ping ; Kotloski, Robert ; Nef, Serge ; Luikart, Bryan W. ; Parada, Luis F. ; McNamara, James O. / Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. In: Neuron. 2004 ; Vol. 43, No. 1. pp. 31-42.
@article{e26b1a33927d484aa70c67d89bed253a,
title = "Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model",
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.",
author = "He, {Xiao Ping} and Robert Kotloski and Serge Nef and Luikart, {Bryan W.} and Parada, {Luis F.} and McNamara, {James O.}",
year = "2004",
month = "7",
day = "8",
doi = "10.1016/j.neuron.2004.06.019",
language = "English (US)",
volume = "43",
pages = "31--42",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model

AU - He, Xiao Ping

AU - Kotloski, Robert

AU - Nef, Serge

AU - Luikart, Bryan W.

AU - Parada, Luis F.

AU - McNamara, James O.

PY - 2004/7/8

Y1 - 2004/7/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=3242704193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242704193&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2004.06.019

DO - 10.1016/j.neuron.2004.06.019

M3 - Article

C2 - 15233915

AN - SCOPUS:3242704193

VL - 43

SP - 31

EP - 42

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 1

ER -