title: Zinc transporter 3 (ZnT3) gene deletion reduces spinal cord white matter damage and motor deficits in a murine MOG-induced multiple sclerosis model.
abstract: The present study aimed to evaluate the role of zinc transporter 3 (ZnT3) on multiple sclerosis (MS) pathogenesis. Experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis, was induced by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) in female mice. Three weeks after the initial immunization, demyelination, immune cell infiltration and blood brain barrier (BBB) disruption in the spinal cord were analyzed. Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. ZnT3 gene deletion profoundly reduced the daily clinical score of EAE. The ZnT3 gene deletion-mediated inhibition of the clinical course of EAE was accompanied by suppression of inflammation and demyelination in the spinal cord. The motor deficit accompanying neuropathological changes associated with EAE were mild in ZnT3 gene deletion mice. This reduction in motor deficit was accompanied by coincident reductions in demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, CD20+ B cells and F4/80+ microglia in the spinal cord. These results demonstrate that ZnT3 gene deletion inhibits the clinical features and neuropathological changes associated with EAE. ZnT3 gene deletion also remarkably inhibited formation of EAE-associated aberrant synaptic zinc patches, matrix metalloproteinases-9 (MMP-9) activation and BBB disruption. Therefore, amelioration of EAE-induced clinical and neuropathological changes by ZnT3 gene deletion suggests that vesicular zinc may be involved in several steps of MS pathogenesis.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: In Yeol
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Kho
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Inha University, Department of Nursing, Incheon, South Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Ulsan University, Department of Neurology, School of Medicine, South Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Koh
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea. Electronic address: swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D004195:Disease Models, Animal; D005260:Female; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000378:metabolism / Q000473:pathology*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C491177:Slc30a3 protein, mouse; C526792:myelin oligodendrocyte glycoprotein (35-50), Ala(37)-
keywords: Blood brain barrier; Experimental autoimmune encephalomyelitis; MMP-9; Multiple sclerosis; Zinc; Zinc transporter