Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory and neuroprotective proteins that are expressed during EAE and MS. We have shown recently that exogenous administration of Zn-MT-II to Lewis rats with EAE significantly reduced clinical symptoms and the inflammatory response, oxidative stress, and apoptosis of the infiltrated central nervous system areas. We show for the first time that Zn-MT-II treatment during EAE significantly prevents demyelination and axonal damage and transection, and stimulates oligodendroglial regeneration from precursor cells, as well as the expression of the growth factors basic fibroblast growth factor (bFGF), transforming growth factor (TGF)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis.
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. M.Penkowa@mai.ku.dk
Milena
M
Penkowa
Juan
J
Hidalgo
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014855:Wallerian Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control
D000975:Antioxidants; D006133:Growth Substances; C021267:zinc thionein; D008668:Metallothionein