Methylene Blue Treatment Enhances Mitochondrial Function and Locomotor Activity in a C57BL/6 Mouse Model of Multiple Sclerosis

Document Type : Original Article


1 College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, Peoples’ Republic of China

2 Transplant Research Center, Shiraz University of Medical Sciences

3 Pharmaceutical Sciences Research Center, Shiraz university of Medical Sciences, Shiraz, Iran

4 Department of Pharmacology-Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center


Multiple sclerosis (MS) is a neurodegenerative disease. Although multiple factors are involved in the pathogenesis of MS, there are several lines of evidence that oxidative stress and mitochondrial dysfunction are involved in neuronal demyelination and deterioration of MS symptoms. Hence, compounds that could modulate mitochondrial function and decrease mitochondria-mediated ROS formation might be able to decrease MS symptoms. Methylene blue (MB) is a compound widely used in the treatment of central nervous system disease (e.g., Alzheimer's disease). It has been found that MB could robustly suppress mitochondria-mediated ROS formation at low concentrations. The current study was designed to evaluate the effect of MB on neuronal demyelination, mitochondrial function, and ROS formation in an animal model of MS. C57BL/6 male mice received cuprizone (0.1% w: w in chow diet for 42 consecutive days). MB (0.5 and 1 mg/kg, oral) was simultaneously administered. Significant demyelination was detected in CPZ-treated animals, which confirm the induction of MS in the mice model. Decreased animals’ locomotor activity, including significant suppression of open field movement, stride length, and decreased time on the rotarod, was evident in CPZ-treated mice. Mitochondrial indices, including significantly elevated lipid peroxidation, mitochondrial depolarization, significant mitochondrial permeabilization, and decreased ATP levels, were also detected in the CPZ group. It was found that MB administration significantly improved animals’ locomotor activity and mitochondrial indices in the current animal model of MS. The effects of MB on mitochondria and mitochondria-mediated ROS formation might play a fundamental role in the protective effects of this compound.