Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

^*Department of Veterinary Morphophysiology and Animal Production, University of Bologna, 40064 Ozzano Emilia, Bologna, Italy; ^‡Pathophysiology Center for the Nervous System, Hesperia Hospital, 41100 Modena, Italy; and ^§Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, 00137 Rome, Italy

Contributed by Rita Levi-Montalcini, October 1, 2004

Abstract

Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor α receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.

Footnotes

↵ ¶ To whom correspondence should be addressed at: DIMORFIPA, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Bologna), Italy. E-mail: lcalza{at}vet.unibo.it.
↵ † M.F. and A.G. contributed equally to this work.
Author contributions: L.G. and L.C. designed research; M.F., A.G., S.P., and G.D. performed research; L.A. contributed new reagents/analytic tools; L.G. and L.C. analyzed data; and L.A., R.L.-M., and L.C. wrote the paper.
Abbreviations: CLSM, confocal laser scan microscopy; DA, Dark Agouti; EAE, experimental allergic encephalomyelitis; MBP, myelin basic protein; MS, multiple sclerosis; OPC, oligodendrocyte precursor cell; PDGF, platelet-derived growth factor; PDGFαR, PDGF α receptor; TH, thyroid hormone; dpi, days postimmunization.
Freely available online through the PNAS open access option.