The underlying hypothesis of the present study is that neurotrophins regulate the survival of peripheral neurons. Unraveling the complex mechanisms regulating neurotrophin expression is critical to the understanding of neuronal survival, aging, and neurodegenerative disease. The processing of neurotrophin gene product results in preproneurotrophin which, following proteolytic cleavage, results in mature neurotrophin. We recently showed that there is little mature nerve growth factor (NGF) and that high molecular weight (MW) NGF species are predominant in peripheral neurons and target tissues. In contrast, we observed that mature neurotrophin-3 (NT-3), along with a high MW precursor, are prevalent in these same peripheral tissues. In addition to NGF and NT-3, both brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) reportedly have regulatory roles in peripheral neurons, yet a thorough characterization of BDNF and NT-4 mRNA and protein expression in these tissues has not been carried out. We provide preliminary evidence, using BDNF and NT-4 enzyme-linked immunosorbant assay (ELISA), for BDNF and NT-4 protein in the superior cervical ganglion (SCG), the sensory trigeminal ganglion, and their peripheral targets, and the potential for regulation of these proteins by NGF. In addition, western analysis revealed the presence of both mature and high MW BDNF and NT-4 species in both the trigeminal and SCG. The overall goal of this project is to characterize BDNF and NT-4 mRNA and protein in young adult peripheral neurons and targets. We will focus on peripheral neurons in the superior cervical ganglion (SCG), trigeminal ganglion, and select peripheral targets, as well as on the preganglionic neurons in the spinal cord that provide innervation to the SCG. Results from these experiments will contribute to the overall understanding of the regulation of adult peripheral neurons. The primary objectives are: 1) Characterize the BDNF and NT-4 protein and mRNA profile in adult peripheral neurons and their targets;2) Determine whether in vivo NGF administration affects BDNF or NT-4 expression in peripheral neurons and targets;3) Characterize the regulatory influences on BDNF and NT-4 protein and mRNA expression;4) Explore the neurotrophin regulation of preganglionic input to the SCG. The results of this project will contribute to our understanding of the complex mechanisms regulating neurotrophin expression, and thus neuronal survival, and will help to determine the factors responsible for the neuronal death that occurs in aging and disease.
The underlying hypothesis of the present study is that neurotrophins regulate the survival of peripheral neurons. Unraveling the complex mechanisms regulating neurotrophin expression is critical to the understanding of neuronal survival, aging, and neurodegenerative disease. The overall goal of this project is to characterize the survival proteins that contribute to the maintenance of young adult peripheral neurons. Our specific hypothesis is that BDNF and NT-4 are involved in the regulation of adult pre-ganglionic and post-ganglionic neurons. Results from these experiments will contribute to the overall understanding of the regulation of adult neurons. The primary objectives are: 1) Characterize brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) protein and mRNA profile in adult peripheral neurons and their targets;2) Determine whether elevated levels of NGF affect BDNF and/or NT-4 expression in peripheral neurons and targets;3) Characterize any regulatory influences on BDNF and NT-4 protein and mRNA expression in peripheral neurons and targets;4) Explore the neurotrophin regulation of preganglionic input to the SCG. The results from this project will contibute to our understanding of the complex mechanisms regulating neurotrophin expression, and thus neuronal survival, and will help to determine the factors responsible for the neuronal death that occurs in aging and disease.
