title: Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation.
abstract: Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.
authors.affiliation: Department of Pediatrics, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Back
authors.forename: Therese M F
authors.initials: TM
authors.lastname: Tuohy
authors.forename: Hanqin
authors.initials: H
authors.lastname: Chen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wallingford
authors.forename: Andrew
authors.initials: A
authors.lastname: Craig
authors.forename: Jaime
authors.initials: J
authors.lastname: Struve
authors.forename: Ning Ling
authors.initials: NL
authors.lastname: Luo
authors.forename: Fatima
authors.initials: F
authors.lastname: Banine
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ansi
authors.initials: A
authors.lastname: Chang
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Bebo
authors.forename: Mahendra S
authors.initials: MS
authors.lastname: Rao
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology; D009836:Oligodendroglia / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid