Time-course of immediate early gene expression in hippocampal subregions of adrenalectomized rats after acute corticosterone challenge

Abstract

Corticosterone hormones mediate the stress response and function in the survival of hippocampal neurons via activation of gluco-(GR) and mineralocorticoid (MR) receptors. Activated GR and MR couple the corticosterone signal through immediate early genes (IEGs) to the late expression of downstream genes, such as neurotrophic factors. The potential importance of IEGs in GR/MR-dependent plasticity in the brain is largely unknown. We examined the region- and time-dependent transcriptional profiles of six IEGs (c-fos, fosB, fra-1, junB, c-jun and egr-1) by in situ hybridization after acute corticosterone challenge in the hippocampus and the primary somatosensory cortex (S1). Adrenalectomized rats and subsequent hormone injections were used as a model system to eliminate interference of endogenous corticosterone on IEG expression. In the hippocampus, a single corticosterone dose (10 mg/kg, s.c.) caused a widespread and transient reduction of fosB mRNA after 0.8 h, whereas changes in both c-fos and fra-1 mRNA levels were restricted to the dentate gyrus region. Corticosterone treatment gave rise to a delayed and significant reduction of junB mRNA signals after 2 h in all hippocampal regions, which reversed to increase at 4 h. c-jun and egr-1 mRNA levels were unaffected by corticosterone treatment. On the contrary, in the S1, IEG expression seems to be unaffected by corticosterone treatment, with the exception of a transient increase of junB transcripts at 0.8 h. The early reduction in c-fos family and junB transcripts may contribute to the GR/MR-dependent changes on hippocampal plasticity and may be dependent on rapid corticosteroid signaling.