Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis induction and assessment by diffusion tensor magnetic resonance imaging.
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.
Harsan
Laura-Adela
LA
UMR 7191, Laboratoire d'Imagerie et de Neurosciences Cognitives, Faculté de Médecine, Université Louis Pasteur and Centre National de la Recherche Scientifique, 67085 Strasbourg, France.
Steibel
Jérôme
J
Zaremba
Anita
A
Agin
Arnaud
A
Sapin
Rémy
R
Poulet
Patrick
P
Guignard
Blandine
B
Parizel
Nathalie
N
Grucker
Daniel
D
Boehm
Nelly
N
Miller
Robert H
RH
Ghandour
M Said
MS
D000818:Animals; D001931:Brain Mapping; D024402:Carbonic Anhydrase II / Q000378:metabolism; D002908:Chronic Disease; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D012794:Sialic Acids / Q000378:metabolism; D013963:Thyroid Hormones / Q000627:therapeutic use*; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood / Q000627:therapeutic use*
D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D018809:Proliferating Cell Nuclear Antigen; C465570:Shh protein, mouse; D012794:Sialic Acids; D013963:Thyroid Hormones; C103469:polysialyl neural cell adhesion molecule; D014284:Triiodothyronine; D003471:Cuprizone; D017493:Leukocyte Common Antigens; D024402:Carbonic Anhydrase II