HF-rTMS treatment ameliorates acute cuprizone- induced demyelination and behavioral deficits

Abstract

Schizophrenia is a complex and severe chronic brain disorder resulting in impaired social function and disruption of the perception of reality. Recent research found that using rTMS as a tool for the treatment of schizophrenia was effective in reducing auditory hallucinations, negative symptoms and working memory problems. The exact mechanism of rTMS remains unclear. Studies have reported abnormalities in the white matter of schizophrenic brains, suggesting the involvement of OL/myelin in the etiopathology of schizophrenia. Indirect evidence suggests rTMS treatment might influence the OL/myelin in brain; no direct research has reported direct effects of rTMS on OL/myelin in schizophrenia. To address this issue, we used animal models of “acute demyelination” and “chronic demyelination” by administration of CPZ. High frequency rTMS (HF-rTMS) was used to treat animals after CPZ exposure began. Behavioral tests, histological staining and western blotting were used to evaluate the efficacy of HF-rTMS. HF-rTMS was found to reverse CPZ-induced behavioral alterations in acute but not chronic demyelination. In acute demyelination, HF-rTMS alleviated CPZ-induced brain demyelination, increased oligodendrocyte progenitor cells in demyelinated sites and decreased astrogliosis in hippocampus. HF-rTMS had no effect on the accumulation of activated microglia in demyelinated sites.