Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 in the adult rat spinal cord: Regulation by the glutamate receptor agonist kainic acid

Previous in vitro studies indicate that select members of the neurotrophin gene family, namely brain-derived neurotrophic factor (BDNF), neurotrophin- 3 (NT-3), and neurotrophin-4/5 (NT-4/5), contribute to survival and differe ntiation of spinal cord motoneurons. To investigate the potential roles of these factors in the adult spinal cord, we examined their cellular localiza tion and regulation after systemic exposure to an excitotoxic stimulus, kai nic acid (KA). Of the neurotrophins examined, NT-4/5 mRNA was most robustly expressed in t he lumbosacral spinal cord of the normal adult rat, including expression by neurons throughout the gray matter, and in a subpopulation of white and gr ay matter glia. Both BDNF and NT-3 mRNAs were also densely expressed by a m otoneurons of lamina IX, but were detected at lower levels elsewhere in the gray matter. NT-3 mRNA was additionally expressed by spinal cord glia, but was less widespread compared to NT-4/5. In response to systemic administra tion of KA, NT-4/5 and BDNF mRNAs were dramatically upregulated in a spatia lly and temporally restricted fashion, whereas levels of NT-3 mRNA were unc hanged. These results provide strong in vivo evidence to support the idea t hat BDNF, NT-3, and in particular, NT-4/5, play a role in the normal functi on of the adult spinal cord. Furthermore, our results indicate that the act ions of BDNF and NT-4/5 participate in the response of the cord to excitoto xic stimuli, and that those of NT-4/5 and NT-3 include both neurons and gli a.