Exercise induces metallothioneins in mouse spinal cord.

Regular exercise has displayed a beneficial effect on the progression of amyotrophic lateral sclerosis (ALS). However, the mechanism is poorly understood. We here present that regular exercise on a treadmill induces metallothioneins (MTs: MT-1, MT-2, and MT-3) in spinal cords of mice. As MTs are strong scavengers of reactive oxygen species and have some neurotrophic activities, exercise may have some beneficial effects on spinal motor neurons in patients with ALS owing to the induction of MTs. The running exercise on a treadmill for 30 min/day increased the mRNA expression levels of MT-1, MT-2, and MT-3 up to 193%, 298%, and 196%, respectively, of the control value 12 h after the start of exercise. After two weeks of daily exercise, Western blotting of the MTs proteins showed that the expression levels of MT-1/2 and MT-3 reached 173% and 146%, respectively, compared with those in sedentary mice. Running exercise on a treadmill for 2 weeks led to the gradual accumulation of MT proteins in the spinal cords of the mice. In addition, MT-1/2 and MT-3 immunoreactivities were enhanced in astrocytes particularly in the gray matter of the spinal cord. We revealed that regular exercise induced transient increases in the expression levels of MT mRNAs and resulted in accumulation of MT proteins in the spinal cords of the normal mice.