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首页> 美国卫生研究院文献>Molecular Therapy >miR-206 Reduces the Severity of Motor Neuron Degeneration in the Facial Nuclei of the Brainstem in a Mouse Model of SMA
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miR-206 Reduces the Severity of Motor Neuron Degeneration in the Facial Nuclei of the Brainstem in a Mouse Model of SMA

机译：MiR-206在SMA小鼠模型中减少了脑干的面部核中的运动神经元变性的严重程度

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Spinal muscular atrophy (SMA) is a severe neuromuscular disease affecting infants caused by alterations of the survival motor neuron gene, which results in progressive degeneration of motor neurons (MNs). Although an effective treatment for SMA patients has been recently developed, the molecular pathway involved in selective MN degeneration has not been yet elucidated. In particular, miR-206 has been demonstrated to play a relevant role in the regeneration of neuromuscular junction in several MN diseases, and particularly it is upregulated in the quadriceps, tibialis anterior, spinal cord, and serum of SMA mice. In the present paper, we demonstrated that miR-206 was transiently upregulated also in the brainstem of the mouse model of SMA, SMAΔ7, in the early phase of the disease paralleling MN degeneration and was down-regulated in the late symptomatic phase. To prevent this downregulation, we intracerebroventricularly injected miR-206 in SMA pups, demonstrating that miR-206 reduced the severity of SMA pathology, slowing down disease progression, increasing survival rate, and improving behavioral performance of mice. Interestingly, exogenous miRNA-206-induced upregulation caused a reduction of the predicted target sodium calcium exchanger isoform 2, NCX2, one of the main regulators of intracellular [Ca2+] and [Na+]. Therefore, we hypothesized that miR-206 might exert part of its neuroprotective effect modulating NCX2 expression in SMA disease.
机译：脊髓肌肉萎缩（SMA）是一种严重的神经肌肉疾病，影响由存活运动神经元基因的改变引起的婴儿，这导致运动神经元（MNS）的进行性退化。虽然最近对SMA患者进行了有效治疗，但尚未阐明参与选择性Mn变性的分子途径。特别地，MiR-206已经证明在几种Mn疾病中的神经肌肉结的再生中发挥相关作用，特别是在Quadriceps，胫骨前，脊髓和SMA小鼠血清中上调。在本文中，我们证明了MIR-206也在SMA，SMAΔ7的小鼠模型的脑干中瞬时上调，在疾病平行Mn变性的早期阶段，在晚期症状期下调。为了防止这种下调，我们在SMA幼崽中脑内注射MIR-206，展示MIR-206降低了SMA病理的严重程度，减缓了疾病进展，增加了生存率，提高了小鼠的行为性能。有趣的是，外源性miRNA-206诱导的上调导致预测的目标钠钙交换剂同种型2，NCX2，细胞内[Ca2 +]和[Na +]之一的降低。因此，我们假设miR-206可能施加其在SMA疾病中调节NCX2表达的一部分其神经保护作用。

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