Voluntary wheel running promotes myelination in the motor cortex through Wnt signaling in mice
Voluntary wheel running promotes myelination in the motor cortex through Wnt signaling in mice
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DOI：
10.1186/s13041-019-0506-8
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发表时间：
2019-10
期刊：
影响因子：
3.6
通讯作者：
Jian Zheng;Xuan Sun;Chao-Lin Ma;Bao-Ming Li;F. Luo
中科院分区：
文献类型：
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作者：
Jian Zheng;Xuan Sun;Chao-Lin Ma;Bao-Ming Li;F. Luo
中枢神经系统髓磷脂具有很强的可塑性，技能学习训练促进少突胶质形成和适应性髓鞘形成。越来越多的证据表明，大脑结构和功能受到体育活动的影响。然而，自愿体育活动对中枢髓鞘形成的影响及其潜在机制尚不清楚。本研究旨在探讨自主轮跑（VWR）对小鼠中枢少突胶质细胞形成和适应性髓鞘形成的影响。将成年C57BL/6 J小鼠置于跑步轮内，进行2周的自主跑步。采用western blotting、qRT-PCR、免疫组化染色和电镜检测中枢神经系统髓磷脂水平。采用免疫组化染色和5-溴-2-脱氧尿苷（BrdU）检测少突胶质细胞前体细胞（OPCs）和少突胶质细胞（OLs）。动物的运动能力采用开阔场地、旋转杆跑和横梁走的行为范式进行测试。检测到Wnt信号的重要分子，并通过OPCs的体外培养验证了这些分子的参与。结果表明，VWR显著增强了运动皮层的髓鞘形成。VWR促进了OPCs的增殖分化，促进了OLs的成熟。vwr调控的髓鞘形成与运动技能的提高和Wnt3a/9a mRNA水平的降低有关，而Wnt3a或Wnt9a刺激Wnt信号通路可抑制体外OPCs的增殖和分化。本研究表明，体育活动通过增强OPCs的增殖和加速髓磷脂的生成，可以高效地促进运动皮层的髓鞘形成，这为理解体育活动对中枢髓鞘形成的有益作用及其潜在机制提供了一步。
Myelin of the central nervous system exhibits strong plasticity, and skill learning exercise promotes oligodendrogenesis and adaptive myelination. Increasing evidence shows that brain structures and functions are affected by physical activity. However, the impact of voluntary physical activity on central myelination and its underlying mechanism remains unclear. The present study aimed to investigate the effect of voluntary wheel running (VWR) on central oligodendrogenesis and adaptive myelination in mice. Adult C57BL/6 J mice were placed in running wheels and allowed for voluntary running 2 weeks. Myelin levels in the central nervous system were detected using western blotting, qRT-PCR, immunohistochemical staining, and electron microscopy. Oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) were detected using immunohistochemical staining and 5-bromo-2-deoxyuridine (BrdU) assays. Motor abilities of the animals were examined using open-field, rotarod running, and beam-walking behavioral paradigms. Vital molecules of Wnt signaling were detected, and the involvement of such molecules was verified using in vitro culture of OPCs. Our results showed that VWR significantly enhanced the myelination in the motor cortex. VWR promoted the proliferation and differentiation of OPCs, and the maturation of OLs. The VWR-regulated myelination was associated with the improved motor skill and decreased mRNA level of Wnt3a/9a, whereas stimulation of Wnt signaling pathway with Wnt3a or Wnt9a suppressed OPCs proliferation and differentiation in vitro. The present study demonstrated that physical activity is highly efficient at promoting myelination in the motor cortex, by enhancing the proliferation of OPCs and accelerating the generation of myelin, providing a step forward in understanding the beneficial effects of physical activity on central myelination and its underlying mechanism.