Evaluation of the protection against oxidative stress mediated by mitochondrial dysfunction and the behavioral properties of a derivative of vitamin E
N. Calvo; G. Walkinshaw; H. Akil
Society for Neuroscience. 2006.
Although mood and anxiety disorders are not regarded as classical mitochondrial diseases, mitochondrial gene expression and function is altered in patients with affective disorders, particularly in those suffering from mood disorders. In view of this evidence, endogenous antioxidants, such as vitamin E could be considered potential agents in the therapeutic treatment of anxiety and clinical depression. We investigated whether a derivative of vitamin E would be able to protect against oxidative stress in a cell-based model of mitochondrial dysfunction and whether it could induce anxiolytic-like or antidepressant-like effects in animal models of psychopathology. Protection against oxidative stress was studied in a Friedrich's Ataxia (FRDA) assay. A better antioxidant efficacy in the FRDA assay is demonstrated by greater ability to increase the survival of FRDA cells 24 h after preincubation with a potential antioxidant compound. In parallel with the biochemical studies, we performed a battery of behavioral tests to evaluate the acute and chronic effects of the vitamin E-derived drug. The tests included animal models of anxiety behavior, depressive-like behavior or motor performance: the Light/Dark box, the Elevated Plus-Maze, the Social Interaction, Forced Swim and Open Field. Appropriate anxiolytic (diazepam) and antidepressant drugs (desipramine, fluoxetine, and imipramine) and the antioxidant Trolox were used as reference in these behavioral assays. Our findings reveal a distinctive profile for the vitamin E derivative and support the view that a compound with the ability to modulate the effects of oxidative stress on survival of cells with altered mitochondrial function/metabolism is also able to modulate emotional behavior. This notion needs to be further tested by using other mitochondria-altered agents.