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

Emily Grace Baxi, Jason T. Schott, Amanda N. Fairchild, Leslie A. Kirby, Rabia Karani, Prech Uapinyoying, Carlos A Pardo-Villamizar, Jeffrey D Rothstein, Dwight E Bergles, Peter Calabresi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1513-1529
Number of pages17
JournalGLIA
Volume62
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Thyroid Hormone Receptors
Oligodendroglia
Rodentia
Hormones
Thyroid Gland
Stem Cells
Myelin Proteins
Occipital Lobe
Corpus Callosum
Neural Conduction
Optic Nerve
Myelin Sheath
Thyroid Hormones
Transgenic Mice
Central Nervous System
GC 1 compound

Keywords

  • GC-1
  • Myelination
  • Oligodendrocytes
  • Thyroid hormone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Medicine(all)

Cite this

A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation. / Baxi, Emily Grace; Schott, Jason T.; Fairchild, Amanda N.; Kirby, Leslie A.; Karani, Rabia; Uapinyoying, Prech; Pardo-Villamizar, Carlos A; Rothstein, Jeffrey D; Bergles, Dwight E; Calabresi, Peter.

In: GLIA, Vol. 62, No. 9, 2014, p. 1513-1529.

Research output: Contribution to journalArticle

Baxi, Emily Grace ; Schott, Jason T. ; Fairchild, Amanda N. ; Kirby, Leslie A. ; Karani, Rabia ; Uapinyoying, Prech ; Pardo-Villamizar, Carlos A ; Rothstein, Jeffrey D ; Bergles, Dwight E ; Calabresi, Peter. / A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation. In: GLIA. 2014 ; Vol. 62, No. 9. pp. 1513-1529.
@article{5540ca8929d24a948c0389577247599d,
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.",
keywords = "GC-1, Myelination, Oligodendrocytes, Thyroid hormone",
author = "Baxi, {Emily Grace} and Schott, {Jason T.} and Fairchild, {Amanda N.} and Kirby, {Leslie A.} and Rabia Karani and Prech Uapinyoying and Pardo-Villamizar, {Carlos A} and Rothstein, {Jeffrey D} and Bergles, {Dwight E} and Peter Calabresi",
year = "2014",
doi = "10.1002/glia.22697",
language = "English (US)",
volume = "62",
pages = "1513--1529",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation

AU - Baxi, Emily Grace

AU - Schott, Jason T.

AU - Fairchild, Amanda N.

AU - Kirby, Leslie A.

AU - Karani, Rabia

AU - Uapinyoying, Prech

AU - Pardo-Villamizar, Carlos A

AU - Rothstein, Jeffrey D

AU - Bergles, Dwight E

AU - Calabresi, Peter

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - GC-1

KW - Myelination

KW - Oligodendrocytes

KW - Thyroid hormone

UR - http://www.scopus.com/inward/record.url?scp=84904277861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904277861&partnerID=8YFLogxK

U2 - 10.1002/glia.22697

DO - 10.1002/glia.22697

M3 - Article

C2 - 24863526

AN - SCOPUS:84904277861

VL - 62

SP - 1513

EP - 1529

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 9

ER -