Abstract
We analyzed the expression of MTs using immunohistochemistry on the spinal cords of patients with ALS (n =12) and controls (n =12). The immunoreactivities of both MT-1/2 and MT-3 stained dominantly in glial cells and were decreased in the spinal cords of patients with ALS, particularly in patients on respirators. The immunoreactivity of MT-1/2 in the ALS groups was significantly reduced compared with controls. In addition, a statistical analysis revealed that the immunoreactivity of MT-3 in astrocytes in the gray matter of the lumbar spinal cord was negatively correlated with the duration of ALS. Both MT-1/2 and MT-3 immunoreactivities were detected mainly in the glias and also detected in some neurons in both control patients and patients with ALS. Interestingly, the patients with MT-3-positive neurons showed definite MT-3-immunoreactive glial reaction around neurons. Previous studies have reported that familial ALS (FALS) model mice (G93A SOD1) crossed with MT-1/2 or MT-3 knock-out mice had accelerated expression of ALS. Judged from these findings, both MT-1/2 and MT-3 play important roles in the progression of ALS. MTs are defensive proteins that can scavenge free radicals; therefore, manipulation of their expression has a strong therapeutic potential for ALS patients.