{"title":"随着年龄增长和耐力训练,神经肌肉接头形态发生变化,从而调节神经肌肉传递和肌纤维组成。","authors":"Tatsuhiro Yamaguchi, Karina Kouzaki, Kazushige Sasaki, Koichi Nakazato","doi":"10.1113/JP285143","DOIUrl":null,"url":null,"abstract":"<p><p>Both ageing and exercise training affect the neuromuscular junction (NMJ) structure. Morphological alterations in the NMJ have been considered to influence neuromuscular transmission and myofibre properties, but the direct link between the morphology and function has yet to be established. We measured the neuromuscular transmission, myofibre composition and NMJ structure of 5-month-old (young) and 24-month-old untrained (aged control) and trained (aged trained) mice. Aged trained mice were subjected to 2 months of endurance training before the measurement. Neuromuscular transmission was evaluated in vivo as the ratio of ankle plantar flexion torque evoked by the sciatic nerve stimulation to that by direct muscle stimulation. The torque ratio was significantly lower in aged mice than in young and aged trained mice at high-frequency stimulations, showing a significant positive correlation with voluntary grip strength. The degree of pre- to post-synaptic overlap of the NMJ was also significantly lower in aged mice and positively correlated with the torque ratio. We also found that the proportion of fast-twitch fibres in the soleus muscle decreased with age, and that age-related denervation occurred preferentially in fast-twitch fibres. Age-related denervation and a shift in myofibre composition were partially prevented by endurance training. These results suggest that age-related deterioration of the NMJ structure impairs neuromuscular transmission and alters myofibre composition, but these alterations can be prevented by structural amelioration of NMJ with endurance training. Our findings highlight the importance of the NMJ as a major determinant of age-related deterioration of skeletal muscles and the clinical significance of endurance training as a countermeasure. KEY POINTS: The neuromuscular junction (NMJ) plays an essential role in neuromuscular transmission and the maintenance of myofibre properties. We show that neuromuscular transmission is impaired with ageing but recovered by endurance training, which contributes to alterations in voluntary strength. Neuromuscular transmission is associated with the degree of pre- to post-synaptic overlap of the NMJ. Age-related denervation of fast-twitch fibres and a shift in myofibre composition toward a slower phenotype are partially prevented by endurance training. Our study provides substantial evidence that age-related and exercise-induced alterations in neuromuscular transmission and myofibre properties are associated with morphological changes in the NMJ.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"107-125"},"PeriodicalIF":4.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alterations in neuromuscular junction morphology with ageing and endurance training modulate neuromuscular transmission and myofibre composition.\",\"authors\":\"Tatsuhiro Yamaguchi, Karina Kouzaki, Kazushige Sasaki, Koichi Nakazato\",\"doi\":\"10.1113/JP285143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Both ageing and exercise training affect the neuromuscular junction (NMJ) structure. Morphological alterations in the NMJ have been considered to influence neuromuscular transmission and myofibre properties, but the direct link between the morphology and function has yet to be established. We measured the neuromuscular transmission, myofibre composition and NMJ structure of 5-month-old (young) and 24-month-old untrained (aged control) and trained (aged trained) mice. Aged trained mice were subjected to 2 months of endurance training before the measurement. Neuromuscular transmission was evaluated in vivo as the ratio of ankle plantar flexion torque evoked by the sciatic nerve stimulation to that by direct muscle stimulation. The torque ratio was significantly lower in aged mice than in young and aged trained mice at high-frequency stimulations, showing a significant positive correlation with voluntary grip strength. The degree of pre- to post-synaptic overlap of the NMJ was also significantly lower in aged mice and positively correlated with the torque ratio. We also found that the proportion of fast-twitch fibres in the soleus muscle decreased with age, and that age-related denervation occurred preferentially in fast-twitch fibres. Age-related denervation and a shift in myofibre composition were partially prevented by endurance training. These results suggest that age-related deterioration of the NMJ structure impairs neuromuscular transmission and alters myofibre composition, but these alterations can be prevented by structural amelioration of NMJ with endurance training. Our findings highlight the importance of the NMJ as a major determinant of age-related deterioration of skeletal muscles and the clinical significance of endurance training as a countermeasure. KEY POINTS: The neuromuscular junction (NMJ) plays an essential role in neuromuscular transmission and the maintenance of myofibre properties. We show that neuromuscular transmission is impaired with ageing but recovered by endurance training, which contributes to alterations in voluntary strength. Neuromuscular transmission is associated with the degree of pre- to post-synaptic overlap of the NMJ. Age-related denervation of fast-twitch fibres and a shift in myofibre composition toward a slower phenotype are partially prevented by endurance training. Our study provides substantial evidence that age-related and exercise-induced alterations in neuromuscular transmission and myofibre properties are associated with morphological changes in the NMJ.</p>\",\"PeriodicalId\":50088,\"journal\":{\"name\":\"Journal of Physiology-London\",\"volume\":\" \",\"pages\":\"107-125\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Physiology-London\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1113/JP285143\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiology-London","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1113/JP285143","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Alterations in neuromuscular junction morphology with ageing and endurance training modulate neuromuscular transmission and myofibre composition.
Both ageing and exercise training affect the neuromuscular junction (NMJ) structure. Morphological alterations in the NMJ have been considered to influence neuromuscular transmission and myofibre properties, but the direct link between the morphology and function has yet to be established. We measured the neuromuscular transmission, myofibre composition and NMJ structure of 5-month-old (young) and 24-month-old untrained (aged control) and trained (aged trained) mice. Aged trained mice were subjected to 2 months of endurance training before the measurement. Neuromuscular transmission was evaluated in vivo as the ratio of ankle plantar flexion torque evoked by the sciatic nerve stimulation to that by direct muscle stimulation. The torque ratio was significantly lower in aged mice than in young and aged trained mice at high-frequency stimulations, showing a significant positive correlation with voluntary grip strength. The degree of pre- to post-synaptic overlap of the NMJ was also significantly lower in aged mice and positively correlated with the torque ratio. We also found that the proportion of fast-twitch fibres in the soleus muscle decreased with age, and that age-related denervation occurred preferentially in fast-twitch fibres. Age-related denervation and a shift in myofibre composition were partially prevented by endurance training. These results suggest that age-related deterioration of the NMJ structure impairs neuromuscular transmission and alters myofibre composition, but these alterations can be prevented by structural amelioration of NMJ with endurance training. Our findings highlight the importance of the NMJ as a major determinant of age-related deterioration of skeletal muscles and the clinical significance of endurance training as a countermeasure. KEY POINTS: The neuromuscular junction (NMJ) plays an essential role in neuromuscular transmission and the maintenance of myofibre properties. We show that neuromuscular transmission is impaired with ageing but recovered by endurance training, which contributes to alterations in voluntary strength. Neuromuscular transmission is associated with the degree of pre- to post-synaptic overlap of the NMJ. Age-related denervation of fast-twitch fibres and a shift in myofibre composition toward a slower phenotype are partially prevented by endurance training. Our study provides substantial evidence that age-related and exercise-induced alterations in neuromuscular transmission and myofibre properties are associated with morphological changes in the NMJ.
期刊介绍:
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.