A Comparative Study of Fluoxetine and Glatiramer Acetate Therapy in the Mouse Model of Multiple Sclerosis

Backgrounds: Multiple sclerosis (MS) is an autoinflammatory disorder of the central nervoussystem which has no certain cure. Glatiramer acetate (GA) is of conventional treatment formultiple sclerosis. Fluoxetine is a selective serotonin reuptake inhibitor and an antidepressantdrug. Several assays represented the immunomodulatory and antioxidant properties ofFluoxetine. This study aims to compare the therapeutic potential of Fluoxetine with GA as thefirst-line treatment of multiple sclerosis.Materials and Methods: In this study, investigation of Fluoxetine and GA effects on the geneexpression profile of some pro-and anti-inflammatory cytokines in C۵۷BL/۶ experimentalautoimmune encephalomyelitis (EAE) model of the disease have been performed. In addition,the extent of demyelination in the corpus callosum of the animals and the phenotype of thedisease were evaluated.Results: In the treatment groups reduction of disease score in comparison to the control groupwas observed. Although both drugs ameliorate clinical symptoms of EAE, GA was moreeffective. Our data revealed that treatment with Fluoxetine and GA resulted in a significantreduction in the expression levels of pro-inflammatory cytokines and a significant increase in theexpression level of anti-inflammatory cytokines. Moreover, the assessment of the antioxidantcapacity of treatments represents a higher expression of Glutathione peroxidase (GPX-۱) in theFluoxetine treated group. Staining by Luxol Fast Blue (LFB) of corpus callosum cross-sectionsaffirmed a significant reduction in the level of demyelination in the treatment groups.Conclusion: The results demonstrated the immunomodulatory and antioxidant effect ofFluoxetine, which has a significant healing influence on the EAE severity. However, morestudies are required to confirm this drug as a first-line treatment of MS.

Keywords:

Multiple sclerosis , Fluoxetine , Glatiramer Acetate , EAE , C۵۷BL/۶