Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-β plus vitamin B12:: Treatment to modify notch-1/sonic hedgehog balance

被引:71
作者
Mastronardi, FG
Min, WX
Wang, HM
Winer, S
Dosch, M
Boggs, JM
Moscarello, MA
机构
[1] Hosp Sick Children, Dept Struct Biol & Biochem, Toronto, ON M5G 1X8, Canada
[2] Hosp Sick Children, Dept Neuropathol, Toronto, ON M5G 1X8, Canada
[3] Hosp Sick Children, Dept Infect Immun Injury & Repair, Toronto, ON M5G 1X8, Canada
关键词
D O I
10.4049/jimmunol.172.10.6418
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interferon-beta is a mainstay therapy of demyelinating diseases, but its effects are incomplete in human multiple sclerosis and several of its animal models. In this study, we demonstrate dramatic improvements of clinical, histological, and laboratory parameters in in vivo mouse models of demyelinating disease through combination therapy with IFN-beta plus vitamin B-12 cyanocobalamin (B12CN) in nonautoimmune primary demyelinating ND4 (DM20) transgenics, and in acute and chronic experimental autoinumme encephalomyelitis in SJL mice. Clinical improvement (p values < 0.0001) was paralleled by near normal motor function, reduced astrocytosis, and reduced demyelination. IFN-beta plus B12CN enhanced in vivo and in vitro oligodendrocyte maturation. In vivo and in vitro altered expression patterns of reduced Notch-1 and enhanced expression of sonic hedgehog and its receptor were consistent with oligodendrocyte maturation andremyelination. IFN-beta-B12CN combination therapy may be promising for the treatment of multiple sclerosis.
引用
收藏
页码:6418 / 6426
页数:9
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