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Glucocorticoid receptor mRNA and protein isoform alterations in the orbitofrontal cortex in schizophrenia and bipolar disorder
Sinclair, D and Webster, MJ and Fullerton, JM and Weickert, CS, Glucocorticoid receptor mRNA and protein isoform alterations in the orbitofrontal cortex in schizophrenia and bipolar disorder, BMC psychiatry ISSN 1471-244X (2012) [Refereed Article]
Copyright 2012 Sinclair et al. Licensed under Creative Commons Attribution 2.0 Generic (CC BY 2.0) https://creativecommons.org/licenses/by/2.0/
Background: The orbitofrontal cortex (OFC) may play a role in the pathogenesis of psychiatric illnesses such as bipolar disorder and schizophrenia, in which hypothalamic-pituitary-adrenal (HPA) axis abnormalities are observed and stress has been implicated. A critical component of the HPA axis which mediates cellular stress responses in the OFC, and has been implicated in psychiatric illness, is the glucocorticoid receptor (GR).
Methods: In the lateral OFC, we employed quantitative real-time PCR and western blotting to investigate GR mRNA and protein expression in 34 bipolar disorder cases, 35 schizophrenia cases and 35 controls. Genotype data for eleven GR gene (NR3C1) polymorphisms was also used to explore possible effects of NR3C1 sequence variation on GR mRNA and protein expression in the lateral OFC.
Results: We found no diagnostic differences in pan GR, GR-1C or GR-1F mRNA expression. However, the GR-1B mRNA transcript variant was decreased (14.3%) in bipolar disorder cases relative to controls (p < 0.05), while GR-1H mRNA was decreased (22.0%) in schizophrenia cases relative to controls (p < 0.005). By western blotting, there were significant increases in abundance of a truncated GRα isoform, putative GRα-D1, in bipolar disorder (56.1%, p < 0.005) and schizophrenia (31.5% p < 0.05). Using genotype data for eleven NR3C1 polymorphisms, we found no evidence of effects of NR3C1 genotype on GR mRNA or GRα protein expression in the OFC.
Conclusions: These findings reveal selective abnormalities of GR mRNA expression in the lateral OFC in psychiatric illness, which are more specific and may be less influenced by NR3C1 genotype than those of the dorsolateral prefrontal cortex reported previously. Our results suggest that the GRα-D1 protein isoform may be up-regulated widely across the frontal cortex in psychiatric illness.
|Item Type:||Refereed Article|
|Keywords:||stress, glucocorticoid, schizophrenia, bipolar disorder|
|Research Division:||Biomedical and Clinical Sciences|
|Research Field:||Cellular nervous system|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Sinclair, D (Dr Duncan Sinclair)|
|Web of Science® Times Cited:||43|
|Deposited By:||Wicking Dementia Research and Education Centre|
|Downloads:||31 View Download Statistics|
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