Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.

Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.
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DOI:
10.1038/s41467-018-05473-1
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发表时间:
2018-08-03
影响因子:
16.6
通讯作者:
Tetzlaff W
Tetzlaff W
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Duncan GJ;Manesh SB;Hilton BJ;Assinck P;Liu J;Moulson A;Plemel JR;Tetzlaff W

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髓鞘再生发生在脊髓损伤(SCI)后,但其功能相关性尚不清楚。我们通过在 SCI 前小鼠血小板源性生长因子受体 α 阳性(PDGFRα 阳性)少突胶质细胞祖细胞 (OPC) 中删除该基因,评估了髓鞘调节因子 (Myrf) 在挫伤性 SCI 后髓鞘再生中的必要性。虽然 SCI 后 Myrf 诱导敲除不会改变 OPC 增殖和密度,但新少突胶质细胞的积累在很大程度上被阻止。这极大地抑制了髓磷脂再生,导致病变中心的有髓轴突减少 44%。然而,SCI 后的自发运动恢复不会因髓鞘再生失败而改变。在具有功能性 MYRF 的对照中,运动恢复先于大多数少突胶质细胞髓磷脂再生的开始。总的来说,这些数据表明,PDGFRα阳性细胞来源的少突胶质细胞中的 MYRF 表达对于挫伤性 SCI 后的髓磷脂再生是必不可少的,但少突胶质细胞髓鞘再生并不是自发恢复行走所必需的。少突胶质细胞对脊髓损伤后功能恢复中髓鞘再生的贡献尚不完全清楚。在这里,作者表明,少突胶质祖细胞分化并不是小鼠脊髓损伤后功能恢复所必需的。
Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely prevented. This greatly inhibits myelin regeneration, resulting in a 44% reduction in myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI is not altered by remyelination failure. In controls with functional MYRF, locomotor recovery precedes the onset of most oligodendrocyte myelin regeneration. Collectively, these data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI but that oligodendrocyte remyelination is not required for spontaneous recovery of stepping. The contribution of oligodendrocytes to remyelination in functional recovery after spinal cord injury is not fully understood. Here, the authors show that oligodendrocyte progenitor cell differentiation is not required for functional recovery after spinal cord injury in mice.
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