The goal of this program is to pursue the research avenues above and, in addition, to explore the potential of limb regeneration blastemas as a source of novel growth factors and the role of macrophages and their products in nerve regeneration. We have proposed that some of these substances, the syntheses of which are dramatically changed in response to axonal injury, attain new and hitherto unknown functions as mediators of the communication between the neuron and its associated cells. Perhaps, these NP and NT also act as trophic factors and regulators of the proliferation and differentiation of Schwann cells during the regeneration process. The main aims of the project are to identify the NP and NT involved, to reveal how their synthesis is regulated, and to find out how, when and where they exert their actions. We use a variety of peripheral nerve preparations including the superior cervical ganglion, the vagus and sciatic nerves and their ganglia, both in vivo and in vitro, to study the expression and regulation of these NP and NT and their receptors.
Methods used are immunocytochemistry, in situ hybridisation, and ligand binding.
We also monitor the effect of the mediators on Schwann cell proliferation, axonal outgrowth, and apoptosis. We expect that the project will give new insights into the intense intercellular communication between the neuron and its associated cells, which is a prerequisite for the initiation and maintenance of the regeneration process.