The effects of acute 17beta-estradiol treatment on gene expression in the young female mouse hippocampus.

Previous studies have demonstrated that treatment with 17beta-estradiol (E(2)) improves both spatial and nonspatial memory in young female mice. Still unclear, however, are the molecular mechanisms underlying the beneficial effects of E(2) on memory. We have previously demonstrated that a single post-training intraperitoneal (i.p.) injection of 0.2 mg/kg E(2) can enhance hippocampal-dependent spatial and object memory consolidation (e.g., Gresack & Frick, 2006b). Therefore, in the present study, we performed a microarray analysis on the dorsal hippocampi of 4-month-old female mice injected i.p. with vehicle or 0.2 mg/kg E(2). Genes were considered differentially expressed following E(2) treatment if they showed a greater than 2-fold change in RNA expression levels compared to controls. Overall, out of a total of approximately 25,000 genes represented on the array, 204 genes showed altered mRNA expression levels upon E(2) treatment, with 111 up-regulated and 93 down-regulated. Of these, 17 of the up-regulated and 6 of the down-regulated genes are known to be involved in learning and memory. mRNA expression changes in 5 of the genes were confirmed by real-time quantitative PCR analysis, and protein changes in these same genes were confirmed by Western blot analysis: Hsp70, a heat shock protein known to be estrogen responsive; Igfbp2, an IGF-I binding protein; Actn4, an actin binding protein involved in protein trafficking; Tubb2a, the major component of microtubules; and Snap25, a synaptosome-specific protein required for neurotransmitter release. The types of genes altered indicate that E(2) may induce changes in the structural mechanics of cells within the dorsal hippocampus that could be conducive to promoting memory consolidation.