Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections.

Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections.
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在皮质脊髓投射缺陷的小鼠中,运动神经元轴突切除术的功能性运动恢复受到损害。

DOI:
10.1371/journal.pone.0101918
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhou L
Zhou L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ding Y;Qu Y;Feng J;Wang M;Han Q;So KF;Wu W;Zhou L

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臂丛神经损伤(BPI)和实验性脊神经根性撕脱伤导致患肢节段运动功能丧失。根撕脱后,通过再次植入撕脱的根,可以恢复显著的运动神经元功能。这种功能恢复在多大程度上依赖于皮质脊髓输入尚不清楚。在这里,我们用Celsr3|Emx1小鼠研究了这个问题,在这些小鼠中,皮质脊髓束(CST)在遗传上是缺失的。在成年小鼠中,我们撕下右侧C5-C7运动和感觉神经根,重新植入右侧C6神经根。行为学研究表明,与对照组相比,Celsr3|Emx1小鼠的肘关节屈曲恢复受到损害。术后5个月,与对照组相比,突变组小轴突数量减少,髓鞘内径与外径之比增大。在术后早期,突变小鼠脊髓中GAP-43的表达和周围神经中髓鞘碱性蛋白(MBP)的表达均低于对照组。五个月后,突变的动物右二头肌萎缩,新形成的神经肌肉连接(NMJ)较少,肌电(EMG)峰峰值(EMG)降低。然而,相当出人意料的是,突变小鼠的运动神经元存活率高于对照小鼠。因此,在根撕脱/再植入后,CST的缺失可能是阻碍轴突再生和再髓鞘形成以及靶神经再支配和新的NMJ形成的重要原因,从而导致功能恢复较低,同时促进运动神经元存活。这些结果表明,操纵皮质脊髓传递可能有助于改善BPI后的功能恢复。
Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.
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具有孤立皮质的小鼠的脊髓成熟和运动。
DOI: 10.1016/j.neuroscience.2013.08.057
发表时间: 2013-12-03
期刊: NEUROSCIENCE
影响因子: 3.3
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