Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients

Psychoneuroendocrinology
M SpiliotakiP Moutsatsou

Abstract

Bipolar disorder (BD) is characterized by hypothalamic pituitary adrenal (HPA) axis hyperactivity, glucocorticoid insensitivity and alterations in serotonin and inflammatory mediators. The glucocorticoid receptor (GR), activator protein-1 (AP-1), nuclear factor-kappa B (NF-kappaB) and c-jun N-terminal kinase (JNK) regulate the above mentioned processes; we therefore assessed their role in BD. Fifteen bipolar depressed patients under multiple anti-depressant therapy, 15 bipolar euthymics under lithium monotherapy and 25 matched controls were studied. Whole cell and nuclear extracts from lymphocytes were immunoblotted for GR, c-fos, JNK and NF-kappaB and nuclear aliquots were submitted to electrophoretic mobility shift assay for GR, AP-1 and NF-kappaB. Associations with the anti-depressant therapy and the state of the disease were also sought. Results, expressed as percentage of pooled protein standard sample intergraded optical density (IOD) (mean +/- SD), revealed: (a) depressed patients had significantly higher GR levels than controls in whole cell (82.63 +/- 6.18 versus 76.27 +/- 4.21%, P < 0.01) and nuclear extracts (86.66 +/- 3.81 versus 81.72 +/- 2.71%, P < 0.001) but lower GR-DNA binding (68.75 +/- 7.91 versus 81.84 +/- 4...Continue Reading

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Citations

Feb 24, 2012·Journal of Neural Transmission·Dragana FilipovićMiroslav Demajo
Dec 18, 2010·Neuromolecular Medicine·Joanna K SoczynskaRoger S McIntyre
Nov 6, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Iva SimicMiroslav Adzic
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