We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Abnormal Glucocorticoid Receptor mRNA and Protein Isoform Expression in the Prefrontal Cortex in Psychiatric Illness.
- Authors
Sinclair, Duncan; Tsai, Shan Yuan; Woon, Heng Giap; Weickert, Cynthia Shannon
- Abstract
Stress has been implicated in the onset and illness course of schizophrenia and bipolar disorder. The effects of stress in these disorders may be mediated by abnormalities of the hypothalamic-pituitary-adrenal axis, and its corticosteroid receptors. We investigated mRNA expression of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and protein expression of multiple GRα isoforms, in the prefrontal cortex of 37 schizophrenia cases and 37 matched controls. Quantitative real-time PCR, western blotting, and luciferase assays were employed. In multiple regression analysis, schizophrenia diagnosis was a significant predictor of total GR mRNA expression (p<0.05), which was decreased (11.4%) in schizophrenia cases relative to controls. No significant effect of diagnosis on MR mRNA was detected. At the protein level, no significant predictors of total GRα protein or the full-length GRα isoform were identified. However, schizophrenia diagnosis was a strong predictor (p<0.0005) of the abundance of a truncated ∼50 kDa GRα protein isoform, putative GRα-D1, which was increased in schizophrenia cases (80.4%) relative to controls. This finding was replicated in a second cohort of 35 schizophrenia cases, 34 bipolar disorder cases, and 35 controls, in which both schizophrenia and bipolar disorder diagnoses were significant predictors of putative GRα-D1 abundance (p<0.05 and p=0.005, respectively). Full-length GRα was increased in bipolar disorder relative to schizophrenia cases. Luciferase assays demonstrated that the GRα-D1 isoform can activate transcription at glucocorticoid response elements. These findings confirm total GR mRNA reductions in schizophrenia and provide the first evidence of GR protein isoform abnormalities in schizophrenia and bipolar disorder.
- Subjects
GLUCOCORTICOID receptors; PREFRONTAL cortex; BIPOLAR disorder; DIAGNOSIS of schizophrenia; MESSENGER RNA; WESTERN immunoblotting
- Publication
Neuropsychopharmacology, 2011, Vol 36, Issue 13, p2698
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/npp.2011.160