title: The expression of metallothioneins is diminished in the spinal cords of patients with sporadic ALS.
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.
authors.affiliation: Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Hozumi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Uchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001344:Autopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D000090023:Metallothionein 3; D051379:Mice; D008875:Middle Aged; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D020033:Protein Isoforms; D008668:Metallothionein