title: Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis.
abstract: Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo, Japan.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Guo
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kohyama
authors.forename: Chikako
authors.initials: C
authors.lastname: Harada
authors.forename: Heather A
authors.initials: HA
authors.lastname: Behanna
authors.forename: D Martin
authors.initials: DM
authors.lastname: Watterson
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009457:Neuroglia / Q000187:drug effects* / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C508492:4,6-diphenyl-3-(4-(pyrimidin-2-yl)piperazin-1-yl)pyridazine; D018925:Chemokines; D007166:Immunosuppressive Agents; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010879:Piperazines; D011724:Pyridazines