Zinc exhibits antidepressant-like activity in preclinical tests (the forced swim test and tail suspension test) and in olfactory bulbectomy and chronic unpredictable stress; two models of depression. Zinc also enhances the treatment of depression in humans. In the present study we evaluated the antidepressant activity of zinc in another model of depression-chronic mild stress (CMS) and the effect of zinc treatment on BDNF protein and the mRNA level. In CMS zinc hydroaspartate (10 mg/kg) exhibited a rapid (after 1 week of treatment) antidepressant-like effect. Chronic treatment with zinc induced a 17-39% increase in the BDNF mRNA and protein level in the hippocampus. These data indicate a rapidly acting antidepressant-like activity of zinc in CMS and the involvement of zinc in the regulation of BDNF.
Affective disorders are a medical condition with a complex biological pattern of etiology, involving genetic and epigenetic factors, along with different environmental stressors. Increasing numbers of studies indicate that induction of oxidative and nitrosative stress (O&NS) pathways, which is accompanied by immune-inflammatory response, might play an important role in the pathogenic mechanisms underlying many major psychiatric disorders, including depression and bipolar disorder. Reactive oxygen and nitrogen species have been shown to impair the brain function by modulating activity of principal neurotransmitter (e.g., glutamatergic) systems involved in the neurobiology of depression. Both preclinical and clinical studies revealed that depression is associated with altered levels of oxidative stress markers and typically reduced concentrations of several endogenous antioxidant compounds, such as glutathione, vitamin E, zinc and coenzyme Q10, or enzymes, including glutathione peroxidase, and with an impairment of the total antioxidant status. These oxidative stress parameters can be normalized by successful antidepressant therapy. On the other hand, some antioxidants (zinc, N-acetylcysteine, omega-3 free fatty acids) may exhibit antidepressant properties or enhance standard antidepressant therapy. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present paper reviews selected animal and human studies providing evidence that oxidative stress is implicated in the pathophysiology and treatment of depression and bipolar disorder.
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