The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model.

Published

Journal Article

The kindling model of epilepsy is a form of neuronal plasticity induced by repeated induction of pathological activity in the form of focal seizures. A causal role for the neurotrophin receptor, tyrosine receptor kinase B, in epileptogenesis is supported by multiple studies of the kindling model. Not only is tyrosine receptor kinase B required for epileptogenesis in this model but enhanced activation of tyrosine receptor kinase B has been identified in the hippocampus in multiple models of limbic epileptogenesis. The neurotrophin ligand mediating tyrosine receptor kinase B activation during limbic epileptogenesis is unknown. We hypothesized that neurotrophin-4 (NT4) activates tyrosine receptor kinase B in the hippocampus during epileptogenesis and that NT4-mediated activation of tyrosine receptor kinase B promotes limbic epileptogenesis. We tested these hypotheses in NT4-deficient mice with a targeted deletion of NT4 gene using the kindling model. The development and persistence of amygdala kindling were examined in wild type (+/+) and NT4 null mutant (-/-) mice. No differences were found between +/+ and -/- mice with respect to any facet of the development or persistence of kindling. Despite the absence of NT4, activation of the tyrosine receptor kinase B receptor in the mossy fiber pathway as assessed by phospho-trk immunohistochemistry was equivalent to that of +/+ mice. Together these findings demonstrate that NT4 is not required for limbic epileptogenesis nor is it required for activation of tyrosine receptor kinase B in hippocampus during limbic epileptogenesis.

Full Text

Duke Authors

Cited Authors

  • He, X-P; Butler, L; Liu, X; McNamara, JO

Published Date

  • August 2006

Published In

Volume / Issue

  • 141 / 1

Start / End Page

  • 515 - 520

PubMed ID

  • 16650613

Pubmed Central ID

  • 16650613

Electronic International Standard Serial Number (EISSN)

  • 1873-7544

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2006.03.020

Language

  • eng