title: Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant.
abstract: Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in naive healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.
authors.affiliation: Department of Neurology and Felsenstein Medical Research Center, Rabin Medical Center, The Sackler School of Medicine, Tel Aviv University, Petah Tikva 49100, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Gilgun-Sherki
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.forename: Daphne
authors.initials: D
authors.lastname: Atlas
authors.forename: Eldad
authors.initials: E
authors.lastname: Melamed
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity*; D063308:Myelin-Oligodendrocyte Glycoprotein; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology
chemical_list: D000975:Antioxidants; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D017382:Reactive Oxygen Species; C487056:N-Acetylcysteinamide; D000111:Acetylcysteine