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Neurotrophic Effects of PEDF in the Cerebellum
Joan P. Schwartz
PEDF acts as a survival factor for cerebellar granule cell neurons (CGCs) in culture as well as protecting them against glutamate toxicity or induced apoptosis. The precise mechanism by which PEDF acts on CGCs is still unknown, and we have used cDNA microarrays to investigate the molecular aspects of the effects of PEDF on these neurons. CGCs were incubated with 4 nM PEDF for 1 or 6 hours on either DIV1 (days in vitro) or DIV8 and compared with cells treated with control urea buffer. Analysis of 1,176 genes on the arrays (Clontech) indicated that up to 10 percent of these genes' expression was altered by PEDF treatment, with more genes affected after 6 hours and in DIV8 cells. RT?PCR confirmed the expression pattern observed on the array for most of these genes. The analysis revealed that certain mRNA species encoding transcription factors, neurotrophic factors, and cytokines and chemokines were increased by PEDF treatment. We have demonstrated that activation of the transcription factor NF-kB underlies the ability of PEDF to prevent CGC death from either apoptosis or glutamate toxicity. Current studies are focusing on the role of the neurotrophic factors, cytokines, and chemokines induced by PEDF in its ability to act as a survival factor for cerebellar granule neurons.