Low-field magnetic stimulation improved cuprizone-induced depression-like symptoms and demyelination in female mice

Depression is a common and disabling comorbidity of multiple sclerosis (MS), with currently no clear guidelines for treatment. Low-field magnetic stimulation (LFMS), a novel non-invasive neuromodulation intervention, has been previously demonstrated to rapidly alleviate mood disorders. The aim of the present study was to investigate the effects of LFMS on depression-like behaviors and demyelination in a well-established mouse model of MS. C57BL/6 female mice were fed a 0.2% cuprizone (CPZ) diet for 3 or 6 weeks to induce acute demyelination. During this time, the mice were treated with either sham or LFMS for 20 min/day, 5 days/week. After 3 or 6 weeks of treatment, behavior was assessed with the open field task, Y-maze and the forced swim test. The prefrontal cortex and hippocampus were then collected to perform immunohistochemistry and western blot analysis to verify myelination status. The CPZ diet did not cause significant locomotor deficits; however, working memory, measured using the Y maze, depression-like behavior and adaptive learning, assayed using the forced swim test, were significantly impaired in these animals. LFMS treatment demonstrated a significant antidepressant-like effect and markedly attenuated the CPZ-induced demyelination in the prefrontal cortex after 3- and 6-weeks of treatment, as observed by changes in myelin basic protein immunostaining and western blot analysis. Therefore, the results of the present study indicated that LFMS may be a promising therapy for demyelinating diseases due to the improvement of depressive symptoms via regulation of myelination in cortical areas.