The effect of lengthening contractions on neuromuscular junction structure in adult and old mice.

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice.
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DOI:
10.1007/s11357-016-9937-7
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发表时间:
2016-08
期刊:
AGE
影响因子:
--
通讯作者:
McArdle, Anne
McArdle, Anne
中科院分区:
医学2区
文献类型:
--
作者:
Vasilaki, Aphrodite;Pollock, Natalie;Giakoumaki, Ifigeneia;Goljanek-Whysall, Katarzyna;Sakellariou, Giorgos K.;Pearson, Timothy;Kayani, Anna;Jackson, Malcolm J.;McArdle, Anne

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年老小鼠的骨骼肌在损伤后完全无法再生。这种失败对于肌肉损失已经很明显的老年人来说可能是灾难性的。成年和老年小鼠收缩引起的损伤后肌纤维的退化和再生已得到很好的表征,但人们对这种形式的损伤后运动神经元和神经肌肉接头(NMJ)的伴随变化知之甚少,尽管有人提出收缩引起的损伤后肌肉的重新神经支配缺陷在肌少症中发挥作用。这项研究可视化并量化了成年和老年 Thy1-YFP 转基因小鼠在收缩引起的肌肉损伤后的再生过程中,趾长伸肌 (EDL) 中运动神经元和 NMJ 的结构变化。数据表明,破坏性收缩方案导致成年小鼠肌肉中的 NMJ 最初受到严重破坏,这种破坏在损伤后 28 天内完全逆转。相比之下,在老年小鼠的静止肌肉中,约 15% 的肌纤维失去神经支配,约 80% 的 NMJ 出现破坏。老小鼠肌肉从收缩引起的损伤中恢复后,去神经纤维和部分去神经纤维的比例保持不变,尽管约 25% 的肌纤维在收缩后 28 天完全丧失。因此,在老年小鼠中,损伤后无法恢复全部肌肉力量的产生似乎并不是由于受损的 NMJ 百分比进一步不足,而是似乎至少部分是由于损伤后肌纤维的完全丧失。
Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damage.
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