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Reduction of TrkB expression de novo in the adult mouse impairs epileptogenesis in the kindling model
Author(s) -
Kotloski Robert,
McNamara James O.
Publication year - 2010
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20673
Subject(s) - epileptogenesis , kindling , tropomyosin receptor kinase b , neuroscience , hippocampus , hippocampal formation , tropomyosin receptor kinase a , kindling model , brain derived neurotrophic factor , neurotrophin , psychology , receptor , neurotrophic factors , chemistry , stimulation , biochemistry
Elucidating the mechanisms of epileptogenesis in molecular terms can identify targets for therapies aimed at preventing epileptogenesis or limiting its progression. Genetic perturbations have implicated signaling by the neurotrophin, BDNF, and its receptor, TrkB, in limbic epileptogenesis. Whether this signaling is critical to epileptogenesis in the adult brain is unclear. We sought to determine whether reduced expression of TrkB de novo in the mature brain is sufficient to impair epileptogenesis in the kindling model. Treatment of adult Act‐CreER TrkB flox/flox mice with tamoxifen resulted in modest reductions of TrkB protein expression de novo in the adult that were detected in hippocampus but not other brain regions. Modest reduction of hippocampal TrkB content inhibited epileptogenesis induced by stimulation of hippocampus or amygdala. The data support the conclusion that reduction of TrkB expression in hippocampus de novo in the mature brain impairs epileptogenesis in the kindling model. These findings advance TrkB and its downstream signaling pathways as attractive targets for limiting the progression of epileptogenesis. © 2009 Wiley‐Liss, Inc.