He X-P, Butler L, Liu X, McNamara J O
Department of Medicine (Neurology), Duke University Medical Center, Bryan Research Building, Room 401, Durham, NC 27710, USA.
Neuroscience. 2006 Aug 11;141(1):515-20. doi: 10.1016/j.neuroscience.2006.03.020. Epub 2006 May 2.
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.
癫痫的点燃模型是一种神经元可塑性形式，由以局灶性癫痫发作形式反复诱导的病理活动引起。神经营养因子受体酪氨酸受体激酶B在癫痫发生中的因果作用得到了对点燃模型的多项研究的支持。在该模型中，酪氨酸受体激酶B不仅是癫痫发生所必需的，而且在多种边缘性癫痫发生模型的海马体中已发现酪氨酸受体激酶B的激活增强。在边缘性癫痫发生过程中介导酪氨酸受体激酶B激活的神经营养因子配体尚不清楚。我们假设神经营养因子-4（NT4）在癫痫发生过程中激活海马体中的酪氨酸受体激酶B，并且NT4介导的酪氨酸受体激酶B激活促进边缘性癫痫发生。我们使用点燃模型在靶向缺失NT4基因的NT4缺陷小鼠中测试了这些假设。在野生型（+/+）和NT4基因敲除突变体（-/-）小鼠中检查杏仁核点燃的发展和持续情况。在点燃的发展或持续的任何方面，+/+和-/-小鼠之间均未发现差异。尽管没有NT4，但通过磷酸化trk免疫组织化学评估，苔藓纤维通路中酪氨酸受体激酶B受体的激活与+/+小鼠相当。这些发现共同表明，边缘性癫痫发生不需要NT4，在边缘性癫痫发生过程中海马体中酪氨酸受体激酶B的激活也不需要NT4。
