Crosstalk between BDNF and TNFα in brain versus serum of the cuprizone-induced multiple sclerosis in C57BL/6 mice

Introduction: Brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNFα) are two critical factors in multiple sclerosis (MS). The aim of the present study is comparing the crosstalk between BDNF and TNFα in the brain versus serum and their effects on recovery of C57BL/6 mice demyelination in cuprizone model. Methods: Fifteen C57BL/6 mice 6-week-old in three different groups were used: control (standard rodent chow), cuprizone-exposed1 (CPZ1; 0.2% cuprizone feeding for 5 weeks) and cuprizone-exposed2 (CPZ2; 0.2% cuprizone feeding for 5 weeks followed by 2 weeks of cuprizone withdrawal). To prove MS induction and cognitive behavioral impairment, Y-maze test and histological studies with luxol fast blue staining were done. The levels of BDNF and TNFα in the brain and serum were measured by ELIZA kits. Results: In the present study, Y-maze test demonstrated that MS significantly impaired the cognitive behavior in both CPZ groups compared to control group. Demyelination in corpus callosum (CC) significantly was higher in the two CPZ groups relative to control group. The brain levels of BDNF significantly decreased while the brain levels of TNFα significantly increased in both CPZ groups compared to control group. Serum levels of BDNF and TNFα significantly increased in CPZ1 group compared to control group. Conclusion: According to the present results, cuprizone-induced MS caused to an extensive demyelination in CC, which led to impaired cognitive behavior. Moreover, brain and serum levels of BDNF and TNFα as well as their crosstalk were affected by cuprizone exposure.