AMELIORATIVE EFFECTS OF DIMETHYL FUMARATE IN ACUTE AND CHRONIC MURINE MODELS OF DEPRESSION
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Depression, a major contributor to the global disease burden, occurs in both adults and children, and is associated with impaired antioxidant defense mechanisms. This study examined the effects of dimethyl fumarate (DMF), a fumaric acid ester with immunomodulatory, anti-inflammatory and antioxidant properties in murine models of depression. In the first phase of the study, mice were treated with the either the vehicle, 50 and 100 mg/kg DMF or 15 mg/kg imipramine and subjected to either the forced swim or tail suspension tests. Thereafter, mice were euthanized and levels of antioxidant markers in isolated brain tissues were assayed. In the second phase of the study, mice were subjected to the chronic unpredictable mild stress regimen for four weeks and treated with the vehicle, DMF or imipramine in the last two weeks of the stress protocol. Forced swim and percentage sucrose preference tests were used for behavioural evaluations. Mice were sacrificed, brain levels of catalase, glutathione, thiobarbituric reactive acid substance and nitrite were quantified. Treatment with DMF significantly (p<0.05) reduced periods of immobility in both the forced swim and tail suspension tests following acute and chronic drug treatment and improved sucrose consumption after exposure to chronic unpredictable mild stress. DMF also significantly improved (p<0.05) levels of antioxidants (catalase and glutathione) while reducing prooxidant biomarkers (thiobarbituric reactive acid substance and nitrite levels) in the brain. DMF ameliorated depression in mice and augmented the antioxidant defense mechanism in the brains of mice subjected to chronic unpredictable mild stress.
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