Triiodothyronine administration ameliorates the demyelination/remyelination ratio in a non-human primate model of multiple sclerosis by correcting tissue hypothyroidism

J Neuroendocrinol. 2011 Sep;23(9):778-90. doi: 10.1111/j.1365-2826.2011.02181.x.

Abstract

Remyelination failure is a key landmark in chronic progression of multiple sclerosis (MS), the most diffuse demyelinating disease in human, but the reasons for this are still unknown. It has been shown that thyroid hormone administration in the rodent models of acute and chronic demyelinating diseases improved their clinical course, pathology and remyelination. In the present study, we translated this therapeutic attempt to experimental allergic encephalomyelitis (EAE) in the non-human primate Callithrix Jacchus (marmoset). We report that short protocols of triiodothyronine treatment shifts the demyelination/remyelination balance toward remyelination, as assessed by morphology, immunohistochemistry and molecular biology, and improves the clinical course of the disease. We also found that severely ill animals display hypothyroidism and severe alteration of deiodinase and thyroid hormone receptor mRNAs expression in the spinal cord, which was completely corrected by thyroid hormone treatment. We therefore suggest that thyroid hormone treatment improves myelin sheath morphology in marmoset EAE, by correcting the dysfunction of thyroid hormone cellular effectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Callithrix
  • Demyelinating Diseases / drug therapy*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental* / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Encephalomyelitis, Autoimmune, Experimental* / physiopathology
  • Female
  • Humans
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / pathology
  • Hypothyroidism / physiopathology
  • Male
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / physiopathology
  • Myelin Sheath / pathology
  • Myelin Sheath / physiology
  • Myelin Sheath / ultrastructure
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Oligodendroglia / cytology
  • Oligodendroglia / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Thyroid Hormones / metabolism
  • Triiodothyronine / therapeutic use*

Substances

  • Biomarkers
  • Thyroid Hormones
  • Triiodothyronine