A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

Abrial, Erika; Lucas, George L.; Scarna, H.; Haddjeri, Nasser; Lambás‐Señas, Laura

doi:10.1007/s12035-011-8210-4

Cited by 32 publications

(27 citation statements)

References 101 publications

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“…All PKC isozymes are highly expressed in the central nervous system, mainly in brain regions involved in mood regulation (Abrial et al, 2011). Some studies showed that prefrontal cortex post-mortem tissue samples from suicide victims with a history of a diagnosis of depression had a decreased activity of PKC (Pandey et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Considering that intracellular signaling pathways that modulate brain BDNF are implicated in antidepressant responses, this study investigated whether signaling pathway inhibitors upstream to BDNF might influence the antidepressant-like effect of zinc, a metal that has been shown to display antidepressant properties. To this end, the influence of i.c.v. administration of H-89 (1μg/site, PKA inhibitor), KN-62 (1μg/site, CAMKII inhibitor), chelerythrine (1μg/site, PKC inhibitor), PD98059 (5μg/site, MEK1/2 inhibitor), U0126 (5μg/site, MEK1/2 inhibitor), LY294002 (10nmol/site, PI3K inhibitor) on the reduction of immobility time in the tail suspension test (TST) elicited by ZnCl2 (10mg/kg, p.o.) was investigated. Moreover, the effect of the combination of sub-effective doses of ZnCl2 (1mg/kg, p.o.) and AR-A014418 (0.001μg/site, GSK-3β inhibitor) was evaluated. The occurrence of changes in CREB phosphorylation and BDNF immunocontent in the hippocampus and prefrontal cortex of mice following ZnCl2 treatment was also investigated. The anti-immobility effect of ZnCl2 in the TST was prevented by treatment with PKA, PKC, CAMKII, MEK1/2 or PI3K inhibitors. Furthermore, ZnCl2 in combination with AR-A014418 caused a synergistic anti-immobility effect in the TST. None of the treatments altered locomotor activity of mice. ZnCl2 treatment caused no alteration in CREB phosphorylation and BDNF immunocontent. The results extend literature data regarding the mechanisms underlying the antidepressant-like action of zinc by indicating that its antidepressant-like effect may be dependent on the activation of PKA, CAMKII, PKC, ERK, and PI3K/GSK-3β pathways. However, zinc is not able to acutely increase BDNF in the hippocampus and prefrontal cortex.

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Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…PKC, a main regulator of the phospholipase C/Ca 2+ system, plays an important role in cell signal transduction (21). Through the PKC/CREB signaling pathway, PKC regulates the excitability of nerve cells and affects the synthesis and release of monoamine neurotransmitters, with a relatively high content in the hippocampus (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of paroxetine on spatial memory function and protein kinase C expression in a rat model of depression

Han

Wang

Bian

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effects of paroxetine on the spatial memory and expression level of protein kinase C (PKC) in a rat model of depression. Rat models of depression were established by chronic unpredictable mild stress. The spatial learning and memory function of the rats were assessed by the Morris water maze test. The expression levels of PKC in the hippocampus were detected by western blotting. The results showed that, compared with the control group, the escape latency was prolonged and the percentage of time in the target quadrant and the number of times the rats crossed the platform were reduced in the model group; however, the impaired spatial learning and memory function in these rat models could be restored by paroxetine, almost to a level comparable with that in the normal control animals. In addition, the expression of PKC in the model group was significantly decreased compared with that in the control group, and the expression could also be elevated by paroxetine treatment. These results suggest an association between PKC levels and the pathogenesis of depression. The application of paroxetine can improve the spatial memory and reverse the changes in PKC levels in the hippocampus in the rat model of depression. The present findings have enhanced the understanding of the pathogenesis of depression, and provide experimental evidence for the treatment of depression with paroxetine.

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“…9–12 PKCα, the most predominant isoenzyme in mouse, 13 rabbit, 14 and human 15 hearts, has been identified as a major regulator of heart contractility, 15,16 platelet aggregation in thrombosis, 17–19 and virtually every development stage of atherosclerotic disease. 20,21 Up-regulation of PKCα has been demonstrated in breast cancer cells, 22,23 melanoma cells, 24 and tissue samples of urinary bladder carcinomas 25 and malignant gliomas.…”

Section: Introductionmentioning

confidence: 99%

Dynamics and Membrane Interactions of Protein Kinase C

Igumenova

2015

Biochemistry

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Protein Kinase C (PKC) is a family of Ser/Thr kinases that regulate a multitude of cellular processes through participation in the phosphoinositide signaling pathway. Significant research efforts have been directed at understanding the structure, function, and regulatory modes of the enzyme since its discovery and identification as the first receptor for tumor-promoting phorbol esters. The activation of PKC involves a transition from the cytosolic auto-inhibited latent form to the membrane-associated active form. The membrane recruitment step is accompanied by the conformational rearrangement of the enzyme, which relieves auto-inhibitory interactions and thereby enables PKC to phosphorylate its targets. The multi-domain structure and intrinsic flexibility of PKC present remarkable challenges and opportunities for the biophysical and structural biology studies of this class of enzymes and their interactions with membranes – the major focus of this Current Topics article. I will highlight the recent advances in the field, outline the current challenges, and identify areas where biophysics and structural biology approaches can provide insight into the isoenzyme-specific regulation of PKC activity.

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A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

Cited by 32 publications

References 101 publications

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Effects of paroxetine on spatial memory function and protein kinase C expression in a rat model of depression

Dynamics and Membrane Interactions of Protein Kinase C

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