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Dysregulation of glucocorticoid receptor co-factors FKBP5, BAG1 and PTGES3 in prefrontal cortex in psychotic illness

Citation

Sinclair, D and Fillman, SG and Webster, MJ and Weickert, CS, Dysregulation of glucocorticoid receptor co-factors FKBP5, BAG1 and PTGES3 in prefrontal cortex in psychotic illness, Scientific reports, 3 pp. 1-10. ISSN 2045-2322 (2013) [Refereed Article]


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Licensed under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) https://creativecommons.org/licenses/by-nc-nd/3.0/

DOI: doi:10.1038/srep03539

Abstract

Molecular abnormalities within the glucocorticoid receptor (GR) stress signaling pathway may confer, or reflect, susceptibility to stress in schizophrenia and bipolar disorder, but the extent of such abnormalities in the brain is not known. Using RNA-Seq and qPCR in two postmortem cohorts totaling 55 schizophrenia, 34 bipolar disorder and 55 control individuals, we identified increased FKBP5 and PTGES3 mRNA expression, and decreased BAG1 mRNA expression, in the prefrontal cortex in schizophrenia cases relative to controls (68.0% [p , 0.001], 26.0% [p , 0.01] and 12.1% [p , 0.05] respectively). We also observed increased FKBP5 and decreased BAG1 mRNA expression in bipolar disorder (47.5% [p , 0.05] and 14.9% [p , 0.005]). There were no diagnostic differences in steady-state FKBP51 protein levels, nor in HSPA1A, HSP90AA1, DNAJB1 or HSPB1 mRNA levels. GR, co-factor and chaperone mRNA levels were strongly correlated. These results reveal coordinated cortical dysregulation of FKBP5, PTGES3, BAG1 and GR genes within the glucocorticoid signaling pathway in psychotic illness.

Item Details

Item Type:Refereed Article
Keywords:stress, glucocorticoid, schizophrenia, FKBP5
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Sinclair, D (Dr Duncan Sinclair)
ID Code:130633
Year Published:2013
Web of Science® Times Cited:33
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2019-02-06
Last Modified:2019-04-08
Downloads:5 View Download Statistics

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