We continued a new line of inquiry into the role of neurotrophic factors in mediating some of the adaptive and maladaptive effects of stress in the brain. To explore the hypothesis that nerve growth factors may provide trophic support in an anterograde fashion, we compared the neuroanatomical pattern of BDNF mRNA and protein in response to electroconvulsive seizures (ECS). Using in situ hybridization, we found that chronic ECS induced BDNF mRNA in the granule neurons of the dentate gyrus. However, immunohistochemistry revealed that ECS increased endogenous BDNF protein in the mossy fibers that project from the dentate gyrus of the CA3 pyramidal layer of the hippocampus. Thus, BDNF support of CA3 pyramidal neurons may be derived in large part from the dentate gyrus, and a decrease in BDNF mRNA in the dentate granule neurons, as occurs during stress, may have detrimental effects on CA3 neurons. Maternal deprivation of rat pups decreased BDNF in the hippocampus, suggesting that adverse early-life experiences may change the expression of growth factors and thereby increase stress responsiveness as an adult. We are currently using differential display PCR to identify novel genes induced by kindling and quenching stimulation in the rat brain. Using primers designed to amplify novel members of the protein kinase C, tyrosine receptor kinase, and calmodulin II kinase families, we have found dozens of possible clones that may contain genes involved in the maintenance of kindling.
