Recovery from Chronic Demyelination by Thyroid Hormone Therapy: Myelinogenesis Induction and Assessment by Diffusion Tensor Magnetic Resonance Imaging
Recovery from Chronic Demyelination by Thyroid Hormone Therapy: Myelinogenesis Induction and Assessment by Diffusion Tensor Magnetic Resonance Imaging
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DOI：
10.1523/jneurosci.4453-08.2008
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发表时间：
2008-12-24
影响因子：
5.3
通讯作者：
Ghandour, M. Said
中科院分区：
文献类型：
--
作者：
Harsan, Laura-Adela;Steibel, Jerome;Ghandour, M. Said
多发性硬化症中髓鞘再生过程的失败导致慢性脱髓鞘斑块的形成，从而导致严重的神经功能缺损。C57 BL/6小鼠的长期cuprizone治疗导致显著的白色物质病理学，其特征在于少突胶质细胞耗竭、不可逆的脱髓鞘和cuprizone戒断后的持续功能缺陷。结合体内扩散张量磁共振成像（DT-MRI）和组织学分析，可以对脱髓鞘进行准确的纵向评估。停药后间隔3周注射三碘甲状腺原氨酸（T（3））激素，可逐渐恢复正常的DT-MRI表型，并伴有临床体征和髓鞘再生的改善。T3的作用不限于髓鞘再生的后期，但增加了sonic hedgehog的表达以及Olig 2（+）和PSA-NCAM（+）前体和增殖细胞的数量。我们的研究结果确立了T3作为成年小鼠脑中少突胶质细胞祖细胞诱导剂的作用，慢性脱髓鞘。
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 T3 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 T3 as an inducer of oligodendrocyte progenitor cells in adult mouse brain following chronic demyelination.