title: Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis.
abstract: OBJECTIVE
  To assess the effects of spermidine on the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), with a focus on optic neuritis often associated with MS and EAE.
  
  
  METHODS
  Myelin oligodendrocyte glycoprotein-induced EAE mice were administered with or without spermidine at 30 mM in drinking water for 25 days. Clinical signs of EAE were scored daily, and visual functions were measured by multifocal electroretinograms. Histopathology analysis of the spinal cord and optic nerve was performed after mice were killed on day 25. Hydrogen peroxide (H(2)O(2)) was detected using the probe 2'-7' dichlorofluorescein diacetate (DCFDA) in the optic nerve. The effect of spermidine on H(2)O(2)-induced retinal ganglion cell apoptosis was investigated by lactate dehydrogenase assay.
  
  
  RESULTS
  Daily clinical scoring revealed that the severity of EAE was significantly attenuated in the spermidine-treated group, which was confirmed by milder demyelination and improved axon survival in the spinal cord of spermidine-treated mice. Visual functions were significantly improved in spermidine-treated mice compared with vehicle-treated mice. Spermidine treatment ameliorated the extent of demyelination in the optic nerve and prevented cell loss in the retinal ganglion cell layer. Furthermore, fewer DCFDA-labeled cells were found in the optic nerve in the spermidine-treated EAE mice, and in vitro analysis revealed that spermidine reduced H(2)O(2)-induced retinal ganglion cell apoptosis, suggesting that spermidine alleviated the severities of EAE, particularly of optic neuritis, by acting as an antioxidant.
  
  
  CONCLUSIONS
  The results from this study suggest that oral spermidine administration could be a useful treatment for MS.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Guo
authors.forename: Chikako
authors.initials: C
authors.lastname: Harada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Namekata
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kimura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mitamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000032:analysis / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000737:chemistry / Q000187:drug effects; D009902:Optic Neuritis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000032:analysis; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013095:Spermidine / Q000627:therapeutic use*; D014792:Visual Acuity / Q000502:physiology
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D013095:Spermidine