Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation

Crossin, Kathryn L.; Tai, Ming Hong; Krushel, Leslie A.; Mauro, Vincent P.; Edelman, Gerald M.

doi:10.1073/pnas.94.6.2687

Cited by 132 publications

(114 citation statements)

References 41 publications

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“…The group of genes downregulated by dexamethasone contains four genes that are related to cell differentiation (Wnt7a, Wnt7b, Sox2, and Trib2). These transcripts may represent a new component in the pathway of GC regulation of astrocytic proliferation and cell fate (Crossin et al, 1997;Yu et al, 2011).…”

Section: Gc Action On the Astrocytic Transcriptomementioning

confidence: 99%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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Chronic opioid use leads to the structural reorganization of neuronal networks, involving genetic reprogramming in neurons and glial cells. Our previous in vivo studies have revealed that a significant fraction of the morphine-induced alterations to the striatal transcriptome included glucocorticoid (GC) receptor (GR)-dependent genes. Additional analyses suggested glial cells to be the locus of these changes. In the current study, we aimed to differentiate the direct transcriptional effects of morphine and a GR agonist on primary striatal neurons and astrocytes. Whole-genome transcriptional profiling revealed that while morphine had no significant effect on gene expression in both cell types, dexamethasone significantly altered the transcriptional profile in astrocytes but not neurons. We obtained a complete dataset of genes undergoing the regulation, which includes genes related to glucose metabolism (Pdk4), circadian activity (Per1) and cell differentiation (Sox2). There was also an overlap between morphine-induced transcripts in striatum and GR-dependent transcripts in cultured astrocytes. We further analyzed the regulation of expression of one gene belonging to both groups, serum and GC regulated kinase 1 (Sgk1). We identified two transcriptional variants of Sgk1 that displayed selective GR-dependent upregulation in cultured astrocytes but not neurons. Moreover, these variants were the only two that were found to be upregulated in vivo by morphine in a GR-dependent fashion. Our data suggest that the morphine-induced, GR-dependent component of transcriptome alterations in the striatum is confined to astrocytes. Identification of this mechanism opens new directions for research on the role of astrocytes in the central effects of opioids. V V C 2013 Wiley Periodicals, Inc.

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Section: Gc Action On the Astrocytic Transcriptomementioning

confidence: 99%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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“…The drug is believed to act through its glucocorticoid receptors found in most neurons and glial cells throughout the brain [18]. These receptors' pathways are involved in the inhibition of astrocyte proliferation [19] and microglial activation [20]. Additionally, as an anti-inflammatory substance, Dex reduces numerous pro-inflammatory cytokines, including IL-1β, IL-6, INF-γ and TNF-α [21].…”

Section: Introductionmentioning

confidence: 99%

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

459

393

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Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be ~50 nm by ellipsometry. We were able to release 0.5 µg/cm 2 Dex in 1 CV cycle and upto 92% Dex after 30 CV cycles. In-vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

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“…Use of the same neurological insult highlights the concentration-dependent effects of GCs on neurological inflammation. Notably, GCs also dose-dependently inhibit astrocyte proliferation (Crossin et al 1997). …”

Section: Just How Anti-inflammatory Are Gcs In the Brain?mentioning

confidence: 99%

An inflammatory review of glucocorticoid actions in the CNS

Sorrells¹,

Sapolsky²

2007

Brain, Behavior, and Immunity

397

283

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In recent years the classic view that glucocorticoids, the adrenal steroids secreted during stress, are universally anti-inflammatory has been challenged at a variety of levels. It was first observed that under some circumstances, acute GC exposure could have pro-inflammatory effects on the peripheral immune response. More recently, chronic exposure to GCs has been found to have pro-inflammatory effects on the specialized immune response to injury in the central nervous system. Here we review the evidence that in some cases, glucocorticoids can increase pro-inflammatory cell migration, cytokine production, and even transcription factor activity in the brain. We consider how these unexpected effects of glucocorticoids can co-exist with their well-established anti-inflammatory properties, as well as the considerable clinical implications of these findings.

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Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation

Cited by 132 publications

References 41 publications

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

An inflammatory review of glucocorticoid actions in the CNS

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