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Glia. 2014 Sep;62(9):1513-29. doi: 10.1002/glia.22697. Epub 2014 May 24.

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

Author information

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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. GLIA 2014;62:1513-1529.

© 2014 Wiley Periodicals, Inc.

KEYWORDS:

GC-1; myelination; oligodendrocytes; thyroid hormone

PMID:
24863526
[PubMed - in process]
PMCID:
PMC4107024
[Available on 2015/9/1]
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