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A selective thyroid hormone ? 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 ? 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 PDGF?R-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 ? 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.

SUBMITTER: Baxi EG 

PROVIDER: S-EPMC4107024 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation.

Baxi Emily G EG   Schott Jason T JT   Fairchild Amanda N AN   Kirby Leslie A LA   Karani Rabia R   Uapinyoying Prech P   Pardo-Villamizar Carlos C   Rothstein Jeffrey R JR   Bergles Dwight E DE   Calabresi Peter A PA  

Glia 20140524 9


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 G  ...[more]

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