Wheel Running Improves Motor Function and Spinal Cord Plasticity in Mice With Genetic Absence of the Corticospinal Tract
Wheel Running Improves Motor Function and Spinal Cord Plasticity in Mice With Genetic Absence of the Corticospinal Tract
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DOI：
10.3389/fncel.2019.00106
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发表时间：
2019-03
影响因子：
5.3
通讯作者：
Wei Zhang;Bing-fen Yang;Huandi Weng;Tao Liu;Lingling Shi;Panpan Yu;K. So;Yibo Qu;Libing Zhou
中科院分区：
文献类型：
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作者：
Wei Zhang;Bing-fen Yang;Huandi Weng;Tao Liu;Lingling Shi;Panpan Yu;K. So;Yibo Qu;Libing Zhou
我们之前的研究表明，先天性皮质脊髓束缺失的突变小鼠会自发重塑运动网络，以部分补偿皮质脊髓束缺失的功能。在这里，我们询问自主轮跑是否可以进一步改善cst缺陷小鼠的运动可塑性。成年突变小鼠被随机分配到可以自由使用轮子的“跑步者”组和不能使用轮子的“非跑步者”组。与非跑步者相比，经过8周的训练，跑步者在精细运动、握力、脚滑错误等方面有显著的改善，这是由肌电记录振幅升高和二头肌神经肌肉连接增加所支持的。在跑步者中，与非跑步者相比，经过12周的运动后，单胺能和红脊髓下行轴突的末端分支在脊柱节段显著增加。5-乙基-2 ' -脱氧尿苷（EDU）标记显示，跑步者的增殖细胞（其中90%为olig2阳性少突胶质细胞祖细胞）比非跑步者多4.8倍。在8周的跑步者中，对脊髓样本进行RNAseq分析，发现404个基因上调，398个基因下调，69个不同表达的基因参与信号转导，其中NF-κB、PI3K-Akt和cAMP信号是3个顶级信号通路。12周的训练诱导突触后密度蛋白95 （PSD95）、突触素38和髓鞘碱性蛋白（MBP）显著升高，但脑源性神经营养因子（BDNF）、胶质细胞系源性神经营养因子（GDNF）和胰岛素样生长因子-1 （IGF-1）没有显著升高。因此，运动训练激活了多种信号通路，有助于神经可塑性和功能改善，并可能减轻患者的运动缺陷。
Our previous studies showed that mutant mice with congenital absence of the corticospinal tract (CST) undergo spontaneous remodeling of motor networks to partially compensate for absent CST function. Here, we asked whether voluntary wheel running could further improve locomotor plasticity in CST-deficient mice. Adult mutant mice were randomly allocated to a “runners” group with free access to a wheel, or a “non-runners” group with no access to a wheel. In comparison with non-runners, there was a significant motor improvement including fine movement, grip strength, decreased footslip errors in runners after 8-week training, which was supported by the elevated amplitude of electromyography recording and increased neuromuscular junctions in the biceps. In runners, terminal ramifications of monoaminergic and rubrospinal descending axons were significantly increased in spinal segments after 12 weeks of exercise compared to non-runners. 5-ethynyl-2′-deoxyuridine (EDU) labeling showed that proliferating cells, 90% of which were Olig2-positive oligodendrocyte progenitors, were 4.8-fold more abundant in runners than in non-runners. In 8-week runners, RNAseq analysis of spinal samples identified 404 genes up-regulated and 398 genes down-regulated, and 69 differently expressed genes involved in signal transduction, among which the NF-κB, PI3K-Akt and cyclic AMP (cAMP) signaling were three top pathways. Twelve-week training induced a significant elevation of postsynaptic density protein 95 (PSD95), synaptophysin 38 and myelin basic protein (MBP), but not of brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and insulin like growth factor-1 (IGF-1). Thus, locomotor training activates multiple signaling pathways, contributes to neural plasticity and functional improvement, and might palliate locomotor deficits in patients.