Physical exercise can improve brain function by altering brain gene expression. The expression mechanisms underlying the brain’s response to exercise still remain unknown. miRNAs as vital regulators of gene expression may be involved in regulation of brain genes in response to exercise. However, as yet, very little is known about exercise-responsive miRNAs in brain. We constructed two comparative small RNA libraries of rat brain from a high-intensity intermittent swimming training (HIST) group and a normal control (NC) group. Using deep sequencing and bioinformatics analysis, we identified 2109 (1700 from HIST, 1691 from NC) known and 55 (50 from HIST, 28 from NC) novel candidate miRNAs. Among them, 34 miRNAs were identified as significantly differentially expressed in response to HIST, 16 were up-regulated and 18 were down-regulated. The results showed that all members of mir-200 family were strongly up-regulated, implying mir-200 family may play very important roles in HIST response mechanisms of rat brain. A total of 955 potential target genes of these 34 exercise-responsive miRNAs were identified from rat genes. Most of them are directly involved in the development and regulatory function of brain or nerve. Many acknowledged exercise-responsive brain genes such as Bdnf, Igf-1, Vgf, Ngf c-Fos, and Ntf3 etc. could be targeted by exercise-responsive miRNAs. Moreover, qRT-PCR and SABC immunohistochemical analysis further confirm the reliability of the expression of miRNAs and their targets. This study demonstrated that physical exercise could induce differential expression of rat brain miRNAs and 34 exercise-responsive miRNAs were identified in rat brain. Our results suggested that exercise-responsive miRNAs could play important roles in regulating gene expression of rat brain in response to exercise.

中文翻译：

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全基因组鉴定的大脑miRNA对褐家鼠的高强度间歇游泳训练的反应，通过深度测序。

体育锻炼可以通过改变大脑基因表达来改善大脑功能。大脑对运动反应的表达机制仍然未知。作为基因表达的重要调节剂的miRNA可能参与大脑基因对运动的调节。然而，到目前为止，关于大脑中的运动反应性miRNA知之甚少。我们从高强度间歇游泳训练（HIST）组和正常对照组（NC）组构建了两个比较的大鼠脑小RNA库。使用深度测序和生物信息学分析，我们确定了2109个已知候选miRNA（HIST为1700，NC为1691）和55个（HIST为50，NC为28）。其中，已鉴定出34种miRNA在响应HIST时显着差异表达，其中16种被上调，而18种被下调。结果表明，mir-200家族的所有成员均被强烈上调，这表明mir-200家族可能在大鼠脑HIST反应机制中起着非常重要的作用。从大鼠基因中鉴定出这34种运动反应性miRNA中的955个潜在靶基因。它们中的大多数直接参与脑或神经的发育和调节功能。运动应答性miRNA可以靶向许多公认的运动应答性大脑基因，例如Bdnf，Igf-1，Vgf，Ngf c-Fos和Ntf3等。此外，qRT-PCR和SABC免疫组织化学分析进一步证实了miRNA及其靶标的表达的可靠性。这项研究证明体育锻炼可以诱导大鼠脑miRNA的差异表达，并且在大鼠脑中鉴定出34种对运动有反应的miRNA。