Axonal regeneration after spinal cord injury (SCI) is difficult to achieve, and no fundamental treatment can be applied in clinical settings. DNA methylation has been suggested to play a role in regeneration capacity and neuronal growth after SCI by controlling the expression of regeneration-associated genes (RAGs). The aim of this study was to examine changes in neuronal DNA methylation status after SCI and to determine whether modulation of DNA methylation with ascorbic acid can enhance neuronal regeneration or functional restoration after SCI. Changes in epigenetic marks (5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC)); the expression of Ten-eleven translocation (Tet) family genes; and the expression of genes related to inflammation, regeneration, and degeneration in the brain motor cortex were determined following SCI. The 5hmC level within the brain was increased after SCI, especially in the acute and subacute stages, and the mRNA levels of Tet gene family members (Tet1, Tet2, and Tet3) were also increased. Administration of ascorbic acid (100 mg/kg) to SCI rats enhanced 5hmC levels; increased the expression of the Tet1, Tet2, and Tet3 genes within the brain motor cortex; promoted axonal sprouting within the lesion cavity of the spinal cord; and enhanced recovery of locomotor function until 12 weeks. In conclusion, we found that epigenetic status in the brain motor cortex is changed after SCI and that epigenetic modulation using ascorbic acid may contribute to functional recovery after SCI.

中文翻译：

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抗坏血酸部分通过表观遗传调节促进脊髓损伤后的功能恢复。

脊髓损伤（SCI）后的轴突再生很难实现，并且在临床环境中无法应用任何根本的治疗方法。通过控制再生相关基因（RAGs）的表达，DNA甲基化已被认为在SCI后的再生能力和神经元生长中起作用。这项研究的目的是检查SCI后神经元DNA甲基化状态的变化，并确定抗坏血酸对DNA甲基化的调节是否可以增强SCI后神经元的再生或功能恢复。表观遗传标记的变化（5-羟甲基胞嘧啶（5hmC）和5-甲基胞嘧啶（5mC））；十11易位的表达（四环素）家族基因；SCI后测定脑运动皮层中与炎症，再生和变性相关的基因的表达。SCI后脑内5hmC水平升高，特别是在急性和亚急性期，Tet的mRNA水平升高基因家族成员（Tet1，Tet2和Tet3）也增加了。给予SCI大鼠抗坏血酸（100 mg / kg）可提高5hmC水平；增加脑运动皮质内Tet1，Tet2和Tet3基因的表达；促进脊髓病变腔内的轴突发芽；并增强运动功能的恢复直至12周。总之，我们发现SCI后大脑运动皮层的表观遗传状态发生了变化，使用抗坏血酸的表观遗传调节可能有助于SCI后的功能恢复。