Neurotrophin regulation of peripheral neurons

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DESCRIPTION (provided by applicant): The underlying hypothesis of the proposed studies is that neurotrophins regulate the activities of adult peripheral neurons. The overall goal of these experiments is to understand the specific mechanisms involved in these regulatory influences. Neurotrophic factors such as nerve growth factor (NGF) and neurotrophin-3 (NT3) are believed to regulate neuronal growth and differentiation of peripheral neurons, yet their regulatory role in the adult is poorly understood. The neurotrophic activities of neurotrophins are mediated by two types of transmembrane receptors--p75, low affinity receptor that binds all neurotrophins, and the trk tyrosine kinase receptor (i.e. trkA, trkC), a family of high affinity neurotrophin receptors, each of which preferentially binds a specific neurotrophin. Using our in vivo model of intracerebroventricular NGF infusion, we have the opportunity to test hypotheses regarding the differential regulation of these receptors by NGF using both morphological and molecular measures. In addition, we hypothesize that exogenous NGF enhances interactions between peripheral neurons and glial support cells, providing evidence that neurotrophin regulation of adult neurons is mediated by paracrine neuronal-glial interactions. We propose experiments that examine intraganglionic communications in both sympathetic and sensory ganglia. The primary objectives are to: 1) determine the influences of exogenous NGF and afferent input on neurotrophin receptor expression by sympathetic neurons; 2) investigate the role of NGF in the enhanced sympathosensory and paracrine interactions in the superior cervical ganglion and the effect of deafferentation; 3) examine the role of NGF on enhanced sympathosensory and paracrine interactions in the trigeminal ganglion and the effect of sympathectomy. These results will provide information regarding the regulatory influences of neurotrophins and will provide support for a role for glial cells in neurotrophin regulation.