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/MRdependent 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.

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

“…The cholesterol biosynthetic pathway also is important for learning/plasticity because of its role in generating membrane for neurite outgrowth and because it provides isoprenoids that modulate long-term potentiation (90, 93). It should be noted, however, that some synaptic and plasticity genes also respond to shorter GC exposures (46, 94, 95) (also see Short-Term CORT Sensitivity column in Supplemental Table 1).…”

“…Moreover, these opposite direction aging changes reflect a relative reversal during aging of the maintenance of neuronal over glial activation by chronic CORT (Figure 2). Interestingly, the impaired activation of plasticity and metabolic processes (37, 49, 72, 91, 92, 94, 95, 109) and excessive activation of glial reactivity/inflammation (16, 69, 85, 110, 116) represent canonical biomarkers of the aging brain, suggesting that alterations in GC signaling may have an important contribution to the brain aging phenotype.…”

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus

“…In the first experiment, following 2 weeks of recovery from surgery, the rats were randomly assigned to either a non-stress (NS) or acute stress (AS) group with a 2-h immobilization condition (IMO, typically between 0900 and 1100 hours), which was determined by previous data for GR-mediated transcripts. 28, 29, 30 In the second experiment, 7 days after lentiviral injection, rats were adrenalectomized (ADX) bilaterally and after another 7 days were randomly assigned to two groups; one group was subjected to 2-h IMO stress and the second subcutaneously injected with CORT (3.0 mg kg −1 in sesame oil; Sigma, St Louis, MO, USA) at a volume adjusted to 1 ml kg −1 body weight. 31 In the third experiment, thirty rats were exposed daily to 2-h IMO stress for 21 consecutive days during which they were randomly assigned to receive daily injection of either fluoxetine (chronic stress plus fluoxetine (CS+F); 10 mg kg −1 , intraperitoneal, dissolved in saline solution, Daewoo Pharmaceuticals, Busan, Korea) or 0.9% saline (chronic stress plus vehicle (CS); 1 ml kg −1 ) 30 min before IMO stress.…”

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

“…The early response genes are known to be triggered by certain hormonal or peptide stimulation (4,12). To better understand the changes in the early response genes in neuronostatin-elicited cardiac contractile response, isolated murine cardiomyocytes were treated with neuronostatin (0.3 nM) for periods of 30 min to 2 h. Total protein was extracted to assess the expression of c-jun, while total RNA was extracted for the real-time assay of c-fos expression.…”