The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model.
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.
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Department of Medicine (Neurology), Duke University Medical Center, Bryan Research Building, Room 401, Durham, NC 27710, USA.
Butler
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Liu
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McNamara
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D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology / Q000528:radiation effects; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D007696:Kindling, Neurologic / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009414:Nerve Growth Factors / Q000172:deficiency / Q000502:physiology*; D020813:Receptor, trkB / Q000378:metabolism*
D009414:Nerve Growth Factors; D020813:Receptor, trkB; C073922:neurotrophin 4