Development of drugs for facilitating brain development and memory/learning

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In a previous study, we have found that short-lasting mild prenatal stress (restraint stress to pregnant rats, 30min/day for 3 days from E15 to E17, 30-min stress group) induces neurotrophic effects on morphology of fetal brain neurons, while long-lasting stress (4 hours/day for 3days from E15 to E17, 4-hrs stress group) causes neurotoxic changes. In addition, we have shown that the 30-min stress group reveals significantly better memory and learning performance in the adult offspring. Based on these results, using DNA tips, the present experiments were performed to identify genes which are involved in the facilitation of development of brain neurons and enhanced cognitive performance.Gene expression in three groups, control, 30-min stress and 4-hrs stress groups was investigated using 3 pieces of DNA tips (Rat Genome U34A, Affymetrix) for each group. The DNA tips used included about 8800 genes. The genes analyzed were receptors (808), channels (187), transporters (138), enzymes (1822), kinases (382), phosphatases (129), and transcription factors (57). The total RNAs extracted from the whole brain and hippocampal tissue of the fetal brains were analyzed. Gene expression was ranked for significance based on replication of data, signal intensity, statistical significance of differences among the three groups. Five to twenty genes that revealed significant increases or decreases in expression in the 30-min stress and 4-hrs stress group as compared to the control group were identified. These genes from the hippocampus included neurotrophic factors, and genes related to Alzheimer disease and neuronal guidance. It is also noted that genes showing significant changes are greatly different between the whole brain and hippocampus.