Gene expression profiling of a number of distinct brain regions under different behavioral and biological states was analyzed using DNA microarray technology. These included hippocampal development, aging process, environ-mental enrichment, fear conditioning, and calorie restriction. Our results identified numerous genes and signal pathways that may play critical roles in learning and memory, brain aging and longevity. Furthermore, chemical genetic approach combined with gene expression profiling analysis was applied to study the molecular mechanisms that contribute to brain dysfunction including Alzheimers diseases, neuronal degeneration and brain aging. These studies not only revealed that a number of genes and signal pathways may have participated in the pathological processes of the brain diseases, but also contributed to the identification of therapeutic targets for drug screening and development.