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Combination therapy of apo-transferrin and thyroid hormones enhances remyelination.
Glia ( IF 5.4 ) Pub Date : 2020-08-20 , DOI: 10.1002/glia.23891
María Victoria Rosato-Siri 1 , Leandro Nazareno Marziali 1 , Vanesa Mattera 1 , Jorge Correale 2 , Juana María Pasquini 2, 3
Affiliation  

The current study presents two different approaches with a view to elucidating the interaction between thyroid hormones (TH) and apo‐transferrin (aTf) and their role in myelination and remyelination. First, in vitro assays were conducted to determine the single and combined effects of aTf and triiodothyronine (T3) on oligodendroglial cell lineage proliferation and oligodendrocyte (OLG) maturation in primary cultures. Results revealed higher proliferation rates upon single aTf treatment but Control values upon T3 and aTf + T3 treatments. In addition, both aTf and T3 accelerated OLG maturation, with the greatest effects being exerted by combined aTf + T3 administration in terms of both myelin basic protein (MBP) expression and morphological complexity. Second, in vivo assays were carried out to establish single and combined effects of aTf and T3, as well as TH receptor (THR) inhibitor I‐850, on remyelination following a CPZ‐induced demyelination protocol. Results showed an increase in myelin deposition and the number of mature remyelinating OLG upon single treatments, but a synergic effect upon combined aTf + T3 treatment which was prevented by THR inhibition. It may be thus concluded that combined treatment yielded the most beneficial effects on OLG maturation parameters in vitro and remyelinating capacity in vivo when compared to single treatments. These findings may help explore the development of new target molecules in the treatment of demyelinating diseases.

中文翻译:

脱辅基转铁蛋白和甲状腺激素的联合治疗可增强髓鞘再生。

目前的研究提出了两种不同的方法,以阐明甲状腺激素 (TH) 和载脂蛋白转铁蛋白 (aTf) 之间的相互作用及其在髓鞘形成和髓鞘再生中的作用。首先,进行体外测定以确定aTf和三碘甲状腺原氨酸(T3)对原代培养中少突胶质细胞谱系增殖和少突胶质细胞(OLG)成熟的单一和联合影响。结果显示单次 aTf 处理后的增殖率较高,但 T3 和 aTf + T3 处理时的对照值。此外,aTf 和 T3 都加速了 OLG 成熟,结合 aTf + T3 给药在髓鞘碱性蛋白 (MBP) 表达和形态复杂性方面发挥的作用最大。其次,进行了体内试验以确定 aTf 和 T3 的单一和联合效应,以及 TH 受体 (THR) 抑制剂 I-850,在 CPZ 诱导的脱髓鞘方案后进行髓鞘再生。结果显示,单次治疗后髓磷脂沉积和成熟的髓鞘再生 OLG 数量增加,但在联合 aTf + T3 治疗时具有协同作用,而 THR 抑制阻止了这种作用。因此可以得出结论,与单一治疗相比,联合治疗对体外 OLG 成熟参数和体内髓鞘再生能力产生了最有益的影响。这些发现可能有助于探索治疗脱髓鞘疾病的新靶分子的开发。但在联合 aTf + T3 治疗时的协同作用被 THR 抑制所阻止。因此可以得出结论,与单一治疗相比,联合治疗对体外 OLG 成熟参数和体内髓鞘再生能力产生了最有益的影响。这些发现可能有助于探索治疗脱髓鞘疾病的新靶分子的开发。但在联合 aTf + T3 治疗时的协同作用被 THR 抑制所阻止。因此可以得出结论,与单一治疗相比,联合治疗对体外 OLG 成熟参数和体内髓鞘再生能力产生了最有益的影响。这些发现可能有助于探索治疗脱髓鞘疾病的新靶分子的开发。
更新日期:2020-08-20
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