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Astrocytes are a neural target of morphine action via glucocorticoid receptor-dependent signaling.
MedLine Citation:
PMID:  23339081     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. © 2013 Wiley Periodicals, Inc.
Authors:
Michal Slezak; Michal Korostynski; Agnieszka Gieryk; Slawomir Golda; Jaroslaw Dzbek; Marcin Piechota; Eliza Wlazlo; Wiktor Bilecki; Ryszard Przewlocki
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-22
Journal Detail:
Title:  Glia     Volume:  -     ISSN:  1098-1136     ISO Abbreviation:  Glia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
Affiliation:
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
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