A genomic approach to investigate neuronal apoptosis

Apoptosis has been postulated to play a possible causal role in the onset of Alzheimer's disease due to shortage of trophic supply, deafferentation and excessive production of free radicals. Many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis. In view of the possible involvement of apoptotic processes in Alzheimer's disease and to begin a comprehensive survey of the gene-based molecular mechanisms that underlie these events we have used genome scale screening by DNA microarray technology in cerebellar granule neurons following serum and potassium deprivation. From the 8740 genes interrogated by the microarrays, 423 genes were found regulated both at the transcriptional and post-transcriptional level and segregated into distinct clusters. Functional clustering based on gene ontologies showed coordinated expression of genes with common biological functions and metabolic pathways. Among the genes implicated in apoptotic cerebellar granule neurons, 70 were in common with those differentially expressed in cortical neurons exposed to amyloid beta-protein, indicating the existence of common mechanisms responsible of neuronal cell death. This new approach offer a genomic view of the changes that accompany neuronal apoptosis and yield new insights into the molecular basis underlying it.