Muscle disuse as hindlimb unloading in early postnatal mice negatively impacts grip strength in adult mice: a pilot study.
Muscle disuse as hindlimb unloading in early postnatal mice negatively impacts grip strength in adult mice: a pilot study.
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出生后早期小鼠后肢卸载导致的肌肉废用会对成年小鼠的握力产生负面影响：一项初步研究。
DOI：
10.1152/japplphysiol.00681.2022
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Drummond,MicahJ
中科院分区：
文献类型：
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作者：
Reidy,PaulT;Smith,AustinD;Jevnikar,BenjaminE;Doctor,AbbasK;Williams,RyanW;Kachulkin,AnthonyA;Monnig,JackieM;Fix,DennisK;Petrocelli,JonathanJ;Mahmassani,ZiadS;McKenzie,AlecI;deHart,NaomiMMP;Drummond,MicahJ
缺乏身体活动对健康有许多不利影响，但早期缺乏身体活动对成年后肌肉健康的影响尚不清楚。出生后早期营养不良的影响会持续到成年，我们认为出生后早期缺乏运动也会产生类似的负面影响。为了验证这一假设，我们将出生后小鼠（~ P28, C57BL/6J）暴露在14天的身体不活动中（断奶后不久，从~ P28至P42日龄），以肌肉废弃和后肢卸载（HU）的形式。在这种早期的身体活动之后，他们被允许正常行走，直到5个月大（P140，成年），然后他们接受了14天的HU，有和没有7天的恢复。然后测试他们的身体机能（握力），并提取肌肉并称重。对这些肌肉横截面进行免疫荧光分析肌纤维横截面面积（fCSA）、巨噬细胞密度（CD68+细胞）和细胞外基质（ECM）面积。肌肉重量、fCSA和肌纤维直径被用来量化肌肉和纤维大小的变化。与年龄匹配的对照组相比，早期不运动（HU）对骨骼肌和肌纤维大小没有显著影响。然而，在早期暴露于HU的人群中，观察到成年握力显著降低。这与肌肉巨噬细胞减少和ECM面积增加有关。早期短时间的不使用会对成年期产生负面的持久影响，影响握力、肌肉巨噬细胞和肌肉成分，导致肌肉质量降低。新的和值得注意的是，我们证明，早期生活的废弃导致成年后握力下降。对肌肉成分的分析表明，没有全肌肉或肌纤维大小的损失，这表明肌肉质量下降，类似于早衰。肌肉质量差的特征是肌肉巨噬细胞和细胞外基质面积的改变。我们证明了这种握力丧失与肌肉巨噬细胞和肌肉中非收缩组织面积之间的有趣相关性。
Physical inactivity has many detrimental effects on health, yet the impact of physical inactivity in early life on muscle health in adulthood remains unknown. Early postnatal malnutrition has prolonged effects into adulthood and we propose that early postnatal (P) physical inactivity would have similar negative effects. To test this hypothesis, we exposed postnatal mice (∼P28, C57BL/6J) to 14 days of physical inactivity (shortly after weaning, from ∼P28 to P42 days of age) in the form of muscle disuse with hindlimb unloading (HU). After this early-life physical inactivity, they were allowed to normally ambulate until 5 mo of age (P140, adulthood) when they underwent 14 days of HU with and without 7-day recovery. They were then tested for physical function (grip strength) and muscles were extracted and weighed. Immunofluorescence was carried out on these muscle cross sections for analysis of myofiber cross-sectional area (fCSA), macrophage density (CD68+cells), and extracellular matrix (ECM) area. Muscle weights and fCSA and myofiber diameter were used to quantify changes in muscle and fiber size. Compared with age-matched controls, no notable effects of early-life physical inactivity (HU) on skeletal muscle and myofiber size were observed. However, a significant reduction in adult grip strength was observed in those exposed to HU early in life. This was associated with reduced muscle macrophages and increased ECM area. Exposure to a short period of early life disuse has negative enduring effects into adulthood impacting grip strength, muscle macrophages, and muscle composition as low muscle quality.NEW & NOTEWORTHYWe demonstrate that early life disuse resulted in less grip strength in adulthood. Analysis of muscle composition demonstrated no loss of whole muscle or myofiber size indicating lower muscle quality akin to premature aging. This poor muscle quality was characterized by altered muscle macrophages and extracellular matrix area. We demonstrate intriguing correlations between this loss of grip strength and muscle macrophages and also area of noncontractile tissue in the muscle.