Regulation of hippocampal α1d adrenergic receptor mRNA by corticosterone in adrenalectomized rats

Abstract

The hippocampal formation receives extensive noradrenergic projections and expresses high levels of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Considerable evidence suggests that the noradrenergic system influences hippocampal corticosteroid receptors. However, there is relatively little data describing the influence of glucocorticoids on noradrenergic receptors in the hippocampal formation. α 1d adrenergic receptor (ADR) mRNA is expressed at high levels in the hippocampal formation, within cells that express MR or GR. In order to determine whether expression of α 1d ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7 or 14 days. Levels of α 1d ADR mRNA were profoundly decreased in hippocampal subfields CA1, CA2 and CA3 and the medial and lateral blades of the dentate gyrus, as early as 1 day after ADX, as determined by in situ hybridization. The effect was specific for the hippocampal formation, with levels of α 1d mRNA unaltered by ADX in the lateral amygdala, reticular thalamic nucleus, retrosplenial cortex or primary somatosensory cortex. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 days. Corticosterone replacement prevented the ADX-induced decrease in hippocampal α 1d ADR mRNA, with the magnitude of effect depending on corticosterone dose and hippocampal subregion. These data indicate that α 1d ADR mRNA expression in the hippocampal formation is highly sensitive to circulating levels of corticosterone, and provides further evidence for a close interaction between glucocorticoids and the noradrenergic system in the hippocampus.

Stress rapidly increases alpha 1d adrenergic receptor mRNA in the rat dentate gyrus

“…However, both MR (or type I corticosteroid receptor) and GR (or type II corticosteroid receptor) are highly expressed in the hippocampal formation (Reul and de Kloet, 1985; Herman et al , 1989), making this a region that is highly susceptible to changes in circulating glucocorticoids (McEwen, 2007). We have previously reported that expression of α 1d ADR mRNA in the hippocampal formation is dependent on circulating levels of corticosterone, with adrenalectomy resulting in a relatively quick and profound decrease in α 1d ADR mRNA expression in all hippocampal subfields and the dentate gyrus, that was restored with corticosterone replacement (Day et al , 2008). Whether the effect of corticosterone on α 1d ADR mRNA is direct or indirect is not known.…”

“…This is consistent with the possibility that corticosterone could regulate expression of α 1d ADR mRNA after stressor exposure. However, the stress-induced increase in α 1d ADR mRNA was observed only in the dentate gyrus, whereas adrenalectomy resulted in a decrease in α 1d ADR mRNA expression in the dentate gyrus and all hippocampal subfields, which was restored with corticosterone replacement (Day et al , 2008). A similar selectivity of effect has been observed following propagation of cortical spreading depression, with increased alpha 1 adrenergic receptor binding reported in the dentate gyrus, but not the CA1 or CA3 regions of the hippocampus (Haghir et al , 2009).…”

“…In vitro experiments have shown that glucocorticoids can upregulate α 1d ADR mRNA expression (Rouppe van der Voort et al , 1999). We have previously demonstrated that levels of α 1d ADR mRNA were profoundly decreased throughout the hippocampus and dentate gyrus as early as 1 day after adrenalectomy, and restored by corticosterone replacement (Day et al , 2008), providing additional evidence for regulation of this receptor by glucocorticoids.…”

Simultaneous Detection of Protein and mRNA in Jurkat and KG‐1a Cells by Mass Cytometry

“…The development of new reagents and improvements in methods are aimed at increasing the sensitivity, specificity, and quantifying RNA in situ hybridization signals (9). Researchers have many options ranging from the type of backbone of the antisense probe (cDNA, RNA (10), synthetic (11)(12)(13)) to the type of detection label (radioactive (14), chromogenic (15), fluorescent (16)). Approaches such as in situ PCR can be used to amplify the target RNA sequences prior to in situ hybridization.…”