Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus.

Published

Journal Article

Genetic and pharmacological perturbations suggest that tyrosine receptor kinase B (trkB) receptor activation promotes limbic epileptogenesis, but whether or where trkB activation occurs during epileptogenesis is uncertain. Because activation of trk receptors involves phosphorylation of specific tyrosine residues (Segal et al., 1996), the availability of antibodies that selectively recognize the phosphorylated form of trk receptors at the Shc site permits an immunohistochemical assessment of trk receptor activation. We reported previously increased phospho-specific trk (p-trk) immunoreactivity in the mossy fiber pathway of the hippocampus during epileptogenesis in rats (Binder et al., 1999b). Because the p-trk antibody does not distinguish among trkA, trkB, and trkC, the identity of the neurotrophin receptor(s) undergoing phosphorylation was uncertain. The development of mice carrying a point mutation of the Shc binding site (Y515F) in the trkB gene (trkB(shc)) provided an opportunity to test the hypothesis that trkB is the neurotrophin receptor undergoing phosphorylation. Epileptogenesis in wild-type (WT) mice was associated with increased p-trk immunoreactivity in both the mossy fiber pathway and CA3 stratum oriens of hippocampus. In contrast, the epileptogenesis-associated increase of p-trk immunoreactivity was reduced in trkB(shc) mutant mice. The development of epileptogenesis as measured by electrophysiological and behavioral indices did not differ between trkB(shc) mutant and WT mice. These data demonstrate that the neurotrophin receptor trkB undergoes phosphorylation in the mossy fiber pathway and CA3 stratum oriens of the hippocampus during limbic epileptogenesis. In addition, the signaling pathways activated by the Shc site of trkB exert no detectable regulatory effects on limbic epileptogenesis.

Full Text

Duke Authors

Cited Authors

  • He, X-P; Minichiello, L; Klein, R; McNamara, JO

Published Date

  • September 2002

Published In

Volume / Issue

  • 22 / 17

Start / End Page

  • 7502 - 7508

PubMed ID

  • 12196573

Pubmed Central ID

  • 12196573

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.22-17-07502.2002

Language

  • eng