Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro

Abstract

Carter BS, Meng F, Thompson RC. Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro. Physiol Genomics 44: 1188 -1200, 2012. First published October 30, 2012 doi:10.1152/physiolgenomics.00097.2012.-While general effects of glucocorticoids are well established, the specific cellular mechanisms by which these hormones exert tissue-dependent effects continue to be elaborated. Diseases that demonstrate altered glucocorticoid signaling have been associated with alterations in astrocytes, yet relatively little is known about the effects of glucocorticoids upon this cell type. We have analyzed mRNA expression patterns following glucocorticoid treatment of mouse primary astrocyte cultures. Microarray analysis of cortical astrocyte cultures treated with dexamethasone over an eight-point, 24 h time course identified 854 unique genes with Նtwofold change in mRNA expression at one or more time points. Clustering analysis associated subsets of these mRNA expression changes with gene ontology categories known to be impacted by glucocorticoids. Numerous mRNAs regulated by dexamethasone were also regulated by the natural ligand corticosterone; all of the mRNAs regulated Նtwofold by corticosterone were substantially attenuated by cotreatment with the glucocorticoid receptor antagonist RU486. Of the mRNAs demonstrating Նtwofold expression change in response to both glucocorticoids, 33 mRNAs were previously associated with glucocorticoid regulation, and 36 mRNAs were novel glucocorticoid targets. All genes tested by qPCR for glucocorticoid regulation in cortical astrocyte cultures were also regulated by glucocorticoids in hippocampal astrocyte cultures (18/ 18). Interestingly, a portion of glucocorticoid-regulated genes were astrocyte enriched; the percentage of astrocyte-enriched genes per total number of regulated genes was highest for the early time points and steadily decreased over the time course. These findings suggest that astrocytes in vitro may initially deploy cell type-specific patterns of mRNA regulatory responses to glucocorticoids and subsequently activate additional cell type-independent responses.

Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: Relevance to depressive-like behavior

“…In the present study, we show that depression-linked neuroinflammation is associated with the activation of microglia toward a pro-inflammatory profile, characterized by the upregulation of the pro-inflammatory and downregulation of the anti-inflammatory genes. Although we cannot rule out the possibility of the involvement of astrocytes in the neuroinflammation establishment after chronic exposure to GCs (Carter et al, 2012), pro-inflammatory activation profile of microglia may account for an important part of the neuroinflammation observed in corticosterone-treated mouse brains. Indeed, we show that ApN has potent anti-inflammatory properties on microglia, which happen to be sufficient to block the brain inflammation elicited by chronic corticosterone exposure.…”

Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes

“…As has previously been suggested, the main component of transcriptional response to adrenal steroids is not neuronal but astroglial [8, 26, 27]. This hypothesis was based on astrocyte-specific gene enrichment (higher level of expression) among glucocorticoid inducible transcripts [26].…”

Chronic glucocorticoids exposure enhances neurodegeneration in the frontal cortex and hippocampus via NLRP-1 inflammasome activation in male mice

“…GR is a member of the nuclear receptor superfamily of ligand-dependent transcription factors and mediates the actions of GCs (Carter et al, 2012). The GR is ubiquitously expressed and is essential for life (Buffo et al, 2010).…”