title: A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation.
abstract: Nerve conduction within the mammalian central nervous system is made efficient by oligodendrocyte-derived myelin. Historically, thyroid hormones have a well described role in regulating oligodendrocyte differentiation and myelination during development; however, it remains unclear which thyroid hormone receptors are required to drive these effects. This is a question with clinical relevance since nonspecific thyroid receptor stimulation can produce deleterious side-effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor β action and a potentially limited side-effect profile, promotes in vitro oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells. In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor cells via PDGFαR-CreER;Rosa26-eYFP double-transgenic mice to examine the effect of GC-1 on cellular fate and find that treatment with GC-1 during developmental myelination promotes oligodendrogenesis within the corpus callosum, occipital cortex and optic nerve. GC-1 was also observed to enhance the expression of the myelin proteins MBP, CNP and MAG within the same regions. These results indicate that a β receptor selective thyromimetic can enhance oligodendrocyte differentiation in vitro and during developmental myelination in vivo and warrants further study as a therapeutic agent for demyelinating models.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Baxi
authors.forename: Jason T
authors.initials: JT
authors.lastname: Schott
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Fairchild
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Kirby
authors.forename: Rabia
authors.initials: R
authors.lastname: Karani
authors.forename: Prech
authors.initials: P
authors.lastname: Uapinyoying
authors.forename: Carlos
authors.initials: C
authors.lastname: Pardo-Villamizar
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Rothstein
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Bergles
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000293:Adolescent; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000503:physiopathology / Q000601:surgery; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000503:physiopathology / Q000601:surgery; D066128:Gray Matter / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology*; D009900:Optic Nerve / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D010636:Phenols / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000085:Acetates; D002491:Central Nervous System Agents; C413355:GC 1 compound; D010636:Phenols; D037042:Thyroid Hormone Receptors beta
keywords: GC-1; myelination; oligodendrocytes; thyroid hormone