How age impairs the response of the neuromuscular junction to nerve transection and repair: An experimental study in rats.

How age impairs the response of the neuromuscular junction to nerve transection and repair: An experimental study in rats.
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DOI:
10.1002/jor.20773
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发表时间:
2009-03
影响因子:
2.8
通讯作者:
Li, Zhongyu
Li, Zhongyu
中科院分区:
医学3区
文献类型:
--
作者:
Apel, Peter J.;Alton, Timothy;Northam, Casey;Ma, Jianjun;Callahan, Michael;Sonntag, William E.;Li, Zhongyu

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年龄是周围神经损伤后临床预后最重要的预测因素。神经肌肉连接处(NMJ)的稳定性被认为是神经肌肉恢复的核心。稳定性的特点是维持运动终板和烟碱乙酰胆碱能受体(nAChR)亚型和肌肉调节因子(mrf)的mRNA上调。本研究的目的是确定年龄对周围神经损伤后突触后NMJ恢复和稳定性的影响。年轻和年老的大鼠进行了胫骨神经的横断和修复。在横断后1、2、4、8或16周,检查腓肠肌电恢复、NMJ碎片和终板面积、mrf和nAChR亚型的mRNA和蛋白质水平。神经损伤后,老年NMJ表现出明显的碎片化和运动终板面积的丧失,而年轻NMJ则保持相对稳定。同时,年龄损害了mrf和nachr的峰值上调。而神经损伤后γ-nAChR和肌生成素的表达不受年龄的影响。这些数据支持了nachr和mrf的上调可能在神经断裂和修复后维持NMJ稳定性中发挥重要作用的说法。此外,γ-nAChR和myogenin的表达似乎并不能预防神经损伤后与年龄相关的NMJ碎片和终板面积的损失。这些老年人NMJ对损伤反应的损害可能导致神经损伤后神经肌肉恢复不良。
Age is the most important predictor of clinical outcome after peripheral nerve injury. The stability of the neuromuscular junction (NMJ) after denervation is thought to be central to neuromuscular recovery. Stability is characterized by maintenance of the motor endplate and mRNA upregulation of the constituent nicotinic acetylcholinergic receptor (nAChR) subtypes and the muscle regulatory factors (MRFs). The purpose of this study was to determine the effect of age on the recovery and stability of the post-synaptic NMJ after peripheral nerve injury. Young and aged rats underwent transection and repair of the tibial nerve. At 1, 2, 4, 8 or 16 weeks following transection, the gastrocnemius was examined for electrical recovery, NMJ fragmentation and endplate area, mRNA and protein levels of the MRFs and nAChR subtypes. After nerve injury, aged NMJ exhibited significant fragmentation and loss of motor endplate area while the young NMJ remained relatively stable. Concomitantly, age impaired peak upregulation of the MRFs and nAChRs. However, expression of γ-nAChR and myogenin after nerve injury was not affected by age. These data support the claim that upregulation of the nAChRs and MRFs may play an important role in maintaining NMJ stability following nerve transection and repair. Furthermore, expression of γ-nAChR and myogenin does not appear to prevent age-related NMJ fragmentation and loss of endplate area after nerve injury. These impairments of the aged NMJ response to injury may contribute to the poor neuromuscular recovery seen after nerve injury in this population.
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发表时间: 2001-09-08
期刊: LANCET
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发表时间: 1980-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
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发表时间: 2005-03-01
影响因子: 2.8
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DOI: 10.1113/jphysiol.1981.sp013679
发表时间: 1981-01-01
影响因子: 5.5
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