Aldosterone selectively increases Na(+)-K(+)-ATPase alpha 3-subunit mRNA expression in rat hippocampus

Abstract

In the brain, corticosteroids bind to intracellular glucocorticoid (GR) and mineralocorticoid (MR) receptors, affecting target gene transcription, and thereby altering neuronal function, including electrophysiological activity. The hippocampus very highly expresses both MR and GR; however, MR-regulated hippocampal transcripts have not yet been described. We investigated the effects of adrenalectomy +/- glucocorticoid or mineralocorticoid replacement on expression of mRNAs encoding alpha-subunit isoforms of Na(+)-K(+)-adenosinetriphosphatase, a critical transmembrane ion gradient-regulating enzyme. Aldosterone significantly increased alpha 3-subunit mRNA expression in dentate gyrus granule cells (62% increase compared with adrenalectomy) and in CA1 and CA4 hippocampal neurons (37 and 38%), but not in CA2, CA3, parietal cortex neurons, or glia. This effect was not reproduced by dexamethasone, and none of the corticosteroid manipulations altered alpha 1- or alpha 2-subunit mRNA expression at any site examined. Aldosterone-mediated upregulation of hippocampal alpha 3-subunit mRNA expression may underlie, at least in part, the specific actions of MR ligands on hippocampal function. The observation that aldosterone differentially affects alpha 3-isoform mRNA expression in distinct neuronal populations, associated with the established aldosterone modulations of alpha 1-isoform mRNA in epithelial cells, supports the presence of cell-specific factors that regulate MR-mediated transcriptional activity.