Li Songlin, Saragovi H Uri, Nedev Hinko, Zhao Chunnian, Racine Ronald J, Fahnestock Margaret
Department of Psychiatry and Behavioral Neurosciences, McMaster University, 1200 Main Street West, Hamilton, ON, Canada L8N 3Z5.
Mol Cell Neurosci. 2005 Jun;29(2):162-72. doi: 10.1016/j.mcn.2005.02.007.
Kindling, an experimental model of epileptogenesis, and activation-induced synaptic reorganization are modulated by nerve growth factor (NGF), but whether NGF acts via its high-affinity receptor TrkA and/or the common neurotrophin receptor p75NTR is unknown. We previously demonstrated, and confirmed in this study, that inhibition of NGF binding to both TrkA and p75NTR inhibited kindling and decreased kindling-induced mossy fiber sprouting. We now report specific inhibition of TrkA.NGF binding, but not p75NTR.NGF binding, retarded perforant path kindling progression. However, mossy fiber sprouting was inhibited by either selective TrkA.NGF or p75NTR.NGF antagonists. Our results suggest that TrkA, but not p75NTR, plays a role in kindling, while both receptors modulate kindling-induced mossy fiber sprouting. This implicates different mechanisms of neurotrophin action on kindling (mediated by TrkA) and neuronal sprouting (mediated by both TrkA and p75NTR) and suggests that sprouting involves kindling-independent neurotrophin action via p75NTR.
点燃效应作为癫痫发生的一种实验模型，以及激活诱导的突触重组，均受神经生长因子（NGF）调节，但NGF是通过其高亲和力受体TrkA和/或共同的神经营养因子受体p75NTR发挥作用尚不清楚。我们之前已证明，并在本研究中得到证实，抑制NGF与TrkA和p75NTR的结合可抑制点燃效应，并减少点燃效应诱导的苔藓纤维出芽。我们现在报告，特异性抑制TrkA.NGF结合而非p75NTR.NGF结合，会延缓穿通通路点燃效应的进展。然而，苔藓纤维出芽可被选择性TrkA.NGF或p75NTR.NGF拮抗剂抑制。我们的结果表明，TrkA而非p75NTR在点燃效应中起作用，而两种受体均调节点燃效应诱导的苔藓纤维出芽。这暗示了神经营养因子对点燃效应（由TrkA介导）和神经元出芽（由TrkA和p75NTR共同介导）的作用机制不同，并表明出芽涉及通过p75NTR的与点燃效应无关的神经营养因子作用。
