Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged gpr27 Knockout Zebrafish.
Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged gpr27 Knockout Zebrafish.
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DOI：
10.3390/biomedicines11071938
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发表时间：
2023-07-07
期刊：
影响因子：
4.7
通讯作者：
Nath, Anjali K.
中科院分区：
文献类型：
--
作者：
Rutkove, Seward B.;Chen, Zsu-Zsu;Pandeya, Sarbesh;Callegari, Santiago;Mourey, Tyler;Nagy, Janice A.;Nath, Anjali K.
关键词：
在脊椎动物的整个生命周期中，骨骼肌的质量和功能逐渐下降。这种与年龄相关的疾病被称为石棺减少症。在人类中，骨质疏松症与跌倒、心血管疾病和各种原因死亡的风险有关。随着世界人口老龄化，预计到2050年全球老年人口将达到20亿人，医疗保健系统的经济负担预计也将大幅增加。目前，还没有针对石棺减少症的药物治疗，而且考虑到衰老研究的长期性，高通量化学筛选在哺乳动物模型中是不切实际的。斑马鱼是一种很有前途的脊椎动物模型，在石棺减少领域可以填补这一空白。在这里，我们开发了一种表面电阻抗肌图(SEIM)平台，用于定量和非侵入性地评估成年斑马鱼(幼年、老年和基因突变动物)的骨骼肌健康。在老年斑马鱼(约85%的寿命)与年轻斑马鱼(约20%的寿命)相比，SEIM参数(2千赫相角、2千赫电抗和2千赫电阻)可以很好地检测到肌肉萎缩(p<；0.000001，q=0.000002；p=0.000004，q=0.000006；p=0.000867，q=0.000683)。此外，这些测量与组织学形态计量学分析确定的肌肉萎缩的形态计量学参数(肌纤维横截面积)有很强的相关性(r=0.831，p=2×10−12；r=0.6959，p=2×10−8；r=0.7220，p=4×10−9)。最后，孤儿G蛋白偶联受体GPR27的基因缺失加剧了老年动物骨骼肌的萎缩，SEIM和组织学都证明了这一点。综上所述，这里的数据表明，表面EIM技术可以有效地区分GPR27KO动物健康的年轻肌肉和骨质化老化的肌肉以及晚期萎缩的肌肉。此外，这些研究显示了EIM值如何与动物的细胞大小相关，这使得利用SEIM作为斑马鱼的“虚拟活检”来非侵入性地评估肌纤维萎缩成为可能，这对肌肉和老年学研究是一种有价值的衡量标准。
Throughout a vertebrate organism’s lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy (p < 0.000001, q = 0.000002; p = 0.000004, q = 0.000006; p = 0.000867, q = 0.000683, respectively). Moreover, these same measurements exhibited strong correlations with an established morphometric parameter of muscle atrophy (myofiber cross-sectional area), as determined by histological-based morphometric analysis (r = 0.831, p = 2 × 10−12; r = 0.6959, p = 2 × 10−8; and r = 0.7220; p = 4 × 10−9, respectively). Finally, the genetic deletion of gpr27, an orphan G-protein coupled receptor (GPCR), exacerbated the atrophy of skeletal muscle in aged animals, as evidenced by both sEIM and histology. In conclusion, the data here show that surface EIM techniques can effectively discriminate between healthy young and sarcopenic aged muscle as well as the advanced atrophied muscle in the gpr27 KO animals. Moreover, these studies show how EIM values correlate with cell size across the animals, making it potentially possible to utilize sEIM as a “virtual biopsy” in zebrafish to noninvasively assess myofiber atrophy, a valuable measure for muscle and gerontology research.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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