Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse
Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse
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DOI：
10.1523/jneurosci.1245-05.2005
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发表时间：
2005-08-17
影响因子：
5.3
通讯作者：
Charbonnier, F
中科院分区：
文献类型：
--
作者：
Grondard, C;Biondi, O;Charbonnier, F
一些研究表明，体育锻炼可能是神经保护，即使在神经肌肉疾病的情况下。在目前的工作中，我们评估了基于跑步的训练对2型脊髓性肌萎缩症（SMA）样小鼠的有效性。本研究中使用的模型是携带一个人SMN2转基因拷贝的SMN（运动神经元存活）缺失小鼠。跑步诱导的益处使2型SMA样小鼠的运动功能和寿命维持了57.3%。我们发现，与未经训练的动物相比，跑步训练的小鼠脊髓腰前角神经元死亡的程度降低。值得注意的是，运动增强了运动神经元的存活。我们发现，跑步介导的神经保护与SMN2基因外显子7的选择性剪接模式的变化有关，导致训练小鼠脊髓中含外显子7的转录物数量增加。此外，在小腿的两块肌肉，慢收缩比目鱼肌和快收缩跖肌的水平上进行的分析表明，在跑步训练的动物中，肌肉表型总体上是保守的。这些数据为运动对SMA的有益影响提供了第一个证据，并可能为人类SMA患者带来重要的治疗进展。
Several studies indicate that physical exercise is likely to be neuroprotective, even in the case of neuromuscular disease. In the present work, we evaluated the efficiency of running-based training on type 2 spinal muscular atrophy (SMA)-like mice. The model used in this study is an SMN (survival motor neuron)-null mouse carrying one copy of a transgene of human SMN2. The running-induced benefits sustained the motor function and the life span of the type 2 SMA-like mice by 57.3%. We showed that the extent of neuronal death is reduced in the lumbar anterior horn of the spinal cord of running-trained mice in comparison with untrained animals. Notably, exercise enhanced motoneuron survival. We showed that the running-mediated neuroprotection is related to a change of the alternative splicing pattern of exon 7 in the SMN2 gene, leading to increased amounts of exon 7-containing transcripts in the spinal cord of trained mice. In addition, analysis at the level of two muscles from the calf, the slow-twitch soleus and the fast-twitch plantaris, showed an overall conserved muscle phenotype in running-trained animals. These data provide the first evidence for the beneficial effect of exercise in SMA and might lead to important therapeutic developments for human SMA patients.