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Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis
Author(s) -
Kaneko Masayuki,
Noguchi Takao,
Ikegami Saori,
Sakurai Takeyuki,
Kakita Akiyoshi,
Toyoshima Yasuko,
Kambe Taiho,
Yamada Mitsunori,
Inden Masatoshi,
Hara Hideaki,
Oyanagi Kiyomitsu,
Inuzuka Takashi,
Takahashi Hitoshi,
Hozumi Isao
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23491
Subject(s) - amyotrophic lateral sclerosis , sod1 , immunohistochemistry , spinal cord , cerebrospinal fluid , homeostasis , pathology , transporter , extracellular , intracellular , medicine , genetically modified mouse , biology , endocrinology , chemistry , microbiology and biotechnology , transgene , neuroscience , biochemistry , gene , disease
The loss of homeostasis of essential metals is associated with various diseases, including neurodegenerative diseases. Previous studies have shown that the levels of zinc (Zn) are significantly higher in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Zn transporters and metallothioneins tightly control intracellular and extracellular Zn levels. This study investigated the protein levels of ZnT, a Zn transporter family, in ALS patients and model mice. The mRNA expression of ZnT1, −3, −4, −5, −6, −7, and −10 was assessed in the spinal cords of human control subjects. ZnT3 and ZnT6 protein levels were significantly diminished in the spinal cords of sporadic ALS patients compared with controls. Furthermore, immunohistochemical staining demonstrated decreased ZnT3 and ZnT6 immunoreactivity in the ventral horn of the spinal cords in ALS patients. Moreover, immunohistochemical analysis revealed that all ZnTs expressed in the spinal cords were localized in a distinct subset of motor neurons. In addition, ZnT3 and ZnT6 protein levels were not altered in SOD1 (G93A) mutant transgenic mice before or after the onset of ALS symptoms compared with controls. These results suggest that ZnT3 and ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients; however, this did not occur merely via loss of motor neurons. © 2014 Wiley Periodicals, Inc.