Control of local NGF mRNA synthesis by preformed factors rapidly released from peripheral nerves

After nerve lesion, a biphasic upregulation of nerve growth factor synthesis occurs in nonneuronal cells. Two fundamentally different regulatory principles underlie this phenomenon. A previously described tissue-extrinsic mechanism depends on macrophages invading the lesioned nerve and their secreted products, such as interleukin 1. It is responsible for the second delayed response. Here we demonstrate a novel mechanism of lesion-induced NGF regulation, which makes use exclusively of tissue-intrinsic elements. Sciatic nerve contains a potent preformed NGF-inducing activity. It is released within minutes after nerve lesion and is responsible for the first rapid NGF increase, which occurs within hours after injury. This type of regulatory mechanism may allow for matching of NGF synthesis with the severity of the lesion.