Differential actions of nerve growth factor receptors TrkA and p75NTR in a rat model of epileptogenesis

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.