title: Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice.
abstract: Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and remyelination. Triiodothyronin (T3) is thought to enhance remyelination in the adult brain by the induction of oligodendrocyte maturation. We investigated additional astrocyte-mediated mechanisms by which T3 might promote remyelination in chronically demyelinated lesions using the cuprizone mouse model. C57BL/6 mice were fed cuprizone for 12 weeks to induce lesions with an impaired remyelination capacity. While the expression of oligodenrocyte progenitor markers, i.e., platelet derived growth factor-α receptor was not affected by T3 administration, myelination status, myelin protein expression as well as total and adult oligodendrocyte numbers were markedly increased compared to cuprizone treated controls. In addition to these effects on oligodendrocyte numbers and function, astrogliosis but not microgliosis was ameliorated by T3 administration. Intermediate filament proteins vimentin and nestin as well as the extracellular matrix component tenascin C were significantly reduced after T3 exposure, indicating additional effects of T3 on astrocytes and astrogliosis. Our data clearly indicate that T3 promotes remyelination in chronic lesions by both enhancing oligodendrocyte maturation and attenuating astrogliosis.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.|Department of Anatomical Sciences, Faculty of Medicine, Gilan University of Medical Sciences, Rasht, Iran.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. ragerdi@tums.ac.ir.
authors.forename: Iraj Ragerdi
authors.initials: IR
authors.lastname: Kashani
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Azimzadeh
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Pasbakhsh
authors.affiliation: Department of Surgery, Ziaian Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Omidi
authors.affiliation: Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Golestani
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005911:Gliosis / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D009185:Myelin Proteins; D014284:Triiodothyronine; D003471:Cuprizone
keywords: Astrogliosis; Cuprizone; Demyelination; Multiple sclerosis; Triiodothyronine