Acute Application of NT-3 on Neonatal Rat Spinal Cords

Neuronal survival, growth and differentiation in the developing brain and spinal cord are dependant upon the presence of specific growth factors called neurotrophins. These include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 and function to regulate neuronal survival and differentiation during the development of the vertebrate nervous system by binding with high affinity to the tyrosine kinase (trk) family of receptors, which includes trkA, trkB and trkC. Neurotrophins can also bind to another receptor type named the p75 receptor of the tumor necrosis family, although binding affinity is rather low. Signaling from this receptor most commonly results in programmed cell death. Neurotrophins may activate trk and p75 receptors individually or simultaneously via complexes known as heterocomplexes. The reason for study of these complexes involves their unique ability to discontinue the apoptotic signaling of p75 . Coupled with the knowledge that trkC interacts exclusively with NT-3, this study aimed at determining whether acute application of NT3 would cause an upregulation of heterocomplexes. This would serve as a mechanism to prevent p75 induced cell death. This is of particular importance in circumstances such as spinal cord injury in which p75 expression is drastically upregulated. It was found that there were no observable differences in the amount of heterocomplex expression between acutely treated neonatal rat spinal cords and control cords, however this project yielded other unexpected yet interesting results. It was noted that labeled heterocomplex tracts possessed an abnormally high number of stained nuclei indicating that these tracts may be highly concentrated on radial glial cells since these are known to serve as guide wires to young, migrating cells.