Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis induction and assessment by diffusion tensor magnetic resonance imaging
Laura-Adela Harsan, Jérôme Steibel, Anita Zaremba, Arnaud Agin, Rémy Sapin, Patrick Poulet, Blandine Guignard, Nathalie Parizel, Daniel Grucker, Nelly Boehm, Robert H Miller, M Said Ghandour, Laura-Adela Harsan, Jérôme Steibel, Anita Zaremba, Arnaud Agin, Rémy Sapin, Patrick Poulet, Blandine Guignard, Nathalie Parizel, Daniel Grucker, Nelly Boehm, Robert H Miller, M Said Ghandour
Abstract
The failure of the remyelination processes in multiple sclerosis contributes to the formation of chronic demyelinated plaques that lead to severe neurological deficits. Long-term cuprizone treatment of C57BL/6 mice resulted in pronounced white matter pathology characterized by oligodendrocyte depletion, irreversible demyelination and persistent functional deficits after cuprizone withdrawal. The use of a combination of in vivo diffusion tensor magnetic resonance imaging (DT-MRI) and histological analyses allowed for an accurate longitudinal assessment of demyelination. Injection of triiodothyronine (T(3)) hormone over a 3 week interval after cuprizone withdrawal progressively restored the normal DT-MRI phenotype accompanied by an improvement of clinical signs and remyelination. The effects of T(3) were not restricted to the later stages of remyelination but increased the expression of sonic hedgehog and the numbers of Olig2(+) and PSA-NCAM(+) precursors and proliferative cells. Our findings establish a role for T(3) as an inducer of oligodendrocyte progenitor cells in adult mouse brain following chronic demyelination.
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Source: PubMed