Antidepressant-like effect of α-tocopherol in a mouse model of depressive-like behavior induced by TNF-α

Abstract

Taking into account that pro-inflammatory cytokines and oxidative and nitrosative stress are implicated in the pathogenesis of depression and that α-tocopherol has antidepressant, anti-inflammatory and antioxidant properties, this study investigated the ability of α-tocopherol to abolish the depressive-like behavior induced by i.c.v. administration of TNF-α in the mouse TST. Additionally, we investigated the occurrence of changes in the levels of Bcl2 and Bax and phosphorylation of GSK-3β (Ser9) in the hippocampus of mice. The administration of TNF-α (0.001fg/site, i.c.v.) increased the immobility time in the TST, which was prevented by the administration of α-tocopherol at the doses of 10, 30 and 100mg/kg (p.o.). Subeffective doses of α-tocopherol (10mg/kg, p.o.) and/or the antidepressants fluoxetine (5mg/kg, p.o.), imipramine (0.1mg/kg, p.o.) and bupropion (1mg/kg, p.o.), the NMDA receptor antagonist MK-801 (0.001mg/kg, p.o.) or the neuronal nitric oxide synthase inhibitor 7-nitroindazole (25mg/kg, i.p.) prevented the depressive-like effect induced by TNF-α. None of the treatments altered the locomotor activity of mice. Treatment with TNF-α and/or α-tocopherol did not alter the levels of Bax and Bcl2 or the phosphorylation of GSK-3β in the hippocampus of mice. Together, our results show a synergistic antidepressant-like effect of α-tocopherol with antidepressants against the depressive-like behavior induced by an inflammatory insult, suggesting that this vitamin may be useful to optimize conventional pharmacotherapy of depression, including depressive states associated with inflammatory conditions.

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

“…These findings corroborate with the behavioral results presented here and with previous studies from our group that showed the reversal effect of ALA on the depressivelike behavior of animals treated with CORT (Silva et al, , 2014. Furthermore, several studies show that antioxidants are able to reverse depressive-like behavior alone or in association with antidepressants (Lobato et al, 2010;Moretti et al, 2012;Mazloom et al, 2013;Manosso et al, 2013;Amr et al, 2013).…”

Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

“…In general, minocycline and cytokine antagonists are effective to block inflammation-induced depression when administered before immune stimulation. The same effect is obtained with a wide variety of anti-inflammatory or anti-oxidant natural compounds, such as curcumin, apigenine, honkiol, xiaobuxin-tang flavonoid extract, perillaldehyde, ginseng saponins, and alpha-tocopherol (Wang et al 2014; Li et al 2015a; Sulakhiya et al 2014; An et al 2015; Ji et al 2014; Kang et al 2011; Manosso et al 2013). However, it is not known whether the anti-inflammatory treatment can block behavioral signs of depression once they have developed.…”

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

“…Antidepressive and antioxidative effects of ascorbic acid have also been reported after a unpredictable chronic mild stress protocol (232). Antidepressant properties have been described for other antioxidants as well (201,211,247,278,285). A randomized, double-blind, placebo-controlled pilot study in humans showed that the addition of vitamin C to antidepressant therapy significantly improved clinical outcomes (10).…”