Phosphorylation status of glucocorticoid receptor, heat shock protein 70, cytochrome c and Bax in lymphocytes of euthymic, depressed and manic bipolar patients

Bei, Ekaterini S.; Salpeas, V.; Pappa, Dimitra; Anagnostara, C.; Alevizos, V.; Moutsatsou, Paraskevi

doi:10.1016/j.psyneuen.2009.03.002

Cited by 32 publications

(24 citation statements)

References 95 publications

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“…Our results indicated that alterations of the glucocorticoid receptor pathway, particularly in its phosphorylation, as well as those that regulate redox balance and initiate/prevent apoptotic processes in the limbic system [8,9,10], closely resembled the alterations described in some clinical studies of depression [11,12]. Therefore, in the current study, our primary aim was to characterize animal behavior that was triggered by chronic social isolation, particularly those aspects that are similar to symptoms of depressive disorders such as anxiety, despair and helplessness symptoms.…”

Section: Introductionsupporting

confidence: 63%

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Djordjević¹,

Djordjević²,

Adžić³

et al. 2012

Neuropsychobiology

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Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology.

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Section: Introductionsupporting

confidence: 63%

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Djordjević¹,

Djordjević²,

Adžić³

et al. 2012

Neuropsychobiology

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“…Lymphocytes from patients with BD have been shown to present decreased expression of the anti-apoptotic factor HSP70 along with reduced BAX levels in the cytosolic fraction, suggesting that it had been translocated to the mitochondria to induce apoptosis (Bei et al, 2009). Moreover, increased apoptotic serum activity has been reported in patients (Politi et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Early apoptosis in peripheral blood mononuclear cells from patients with bipolar disorder

Fries

Vasconcelos-Moreno

Gubert

et al. 2014

Journal of Affective Disorders

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“…GR phosphorylation at serine 226 was shown to blunt hormone signalling by enhancing nuclear export of the GR and inhibiting GR transcriptional activity (Galliher-Beckley and Cidlowski 2009), thus possibly contributing to glucocorticoid resistance. Bei et al (2009) observed a signifi cant increase of nuclear pGR-211 levels in lymphocytes of depressed patients with bipolar disorder. Likewise, we have recently shown that GR phosphorylation, evaluated through levels of nuclear pGR-211 and pGR-226, was altered in patients with major depressive disorder (MDD) compared to healthy controls (Simic et al 2013a).…”

Section: Introductionmentioning

confidence: 89%

The role of glucocorticoid receptor phosphorylation in the model of negative affective states

Jovičić

Maric

Soldatović

et al. 2015

The World Journal of Biological Psychiatry

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Phosphorylation status of glucocorticoid receptor, heat shock protein 70, cytochrome c and Bax in lymphocytes of euthymic, depressed and manic bipolar patients

Cited by 32 publications

References 95 publications

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Early apoptosis in peripheral blood mononuclear cells from patients with bipolar disorder

The role of glucocorticoid receptor phosphorylation in the model of negative affective states

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