Chronic unpredictable stress alters gene expression in rat single dentate granule cells.

The rat adrenal hormone corticosterone binds to low and high affinity receptors, discretely localized in brain, including the dentate gyrus. Differential activation of the two receptor types under physiological conditions alters gene expression and functional characteristics of hippocampal neurones. In the present study we examined gene expression of electrophysiologically identified dentate granule cells, 1 day after 21 days of unpredictable stress or control treatment, both under basal corticosteroid conditions and after brief in vitro exposure to a high dose of corticosterone. From each cell, RNA was collected, linearly amplified and hybridized with cDNA clones for three calcium channel subunits, four NMDA, two AMPA and 11 GABA receptor subunits. We found that gene expression was not extensively changed after chronic stress when neurones were studied under basal corticosteroid conditions. However, combined with acute exposure to a high corticosterone dose, relative expression of eight transcripts was significantly altered, including a consistent up-regulation of GABAa receptor alpha 1 and down-regulation of calcium channel alpha 1A and alpha 1G subunit expression. If translated to the protein level, this may result in more transient GABAa receptor mediated responses and less transient calcium influx. This could contribute to enhanced excitability and vulnerability of granule cells after chronic stress.