Uno Hiroyuki, Kamiya Shohei, Akimoto Ryuji, Hosoki Katsu, Tadano Shunta, Isemura Mako, Kouzaki Karina, Tamura Yuki, Kotani Takaya, Nakazato Koichi
HOMERION LABORATORY Co., Ltd., Shinsen 17-2, Shibuya-Ku, Tokyo, 150-0045, Japan.
School of Health and Sport Science, Nippon Sport Science University, 7-1-1 Fukazawa, Setagaya-Ku, Tokyo, 158-8508, Japan.
Sci Rep. 2024 Mar 11;14(1):5848. doi: 10.1038/s41598-024-56382-x.
Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague-Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon.
腰带电极-骨骼肌电刺激(B-SES)是指使用带状电极同时收缩多个肌肉群。已证实抽搐收缩可预防大鼠去神经支配引起的肌肉萎缩,可能是通过线粒体生物合成实现的。本研究探讨了用B-SES诱导强直收缩是否能抑制肌肉萎缩,并确定其潜在的分子机制。我们使用连接在两个踝关节上的腰带电极,评估急性(60Hz,5分钟)和慢性(60Hz,5分钟,每隔一天进行一周)B-SES对Sprague-Dawley大鼠胫前肌(TA)和腓肠肌(GAS)的影响。急性刺激后,左右TA和GAS的糖原含量均显著降低,表明B-SES可引起多个肌肉群同时收缩。B-SES增强了p70S6K磷酸化,这是雷帕霉素复合物1活性机制靶点的一个指标。在慢性刺激期间,将大鼠分为对照组(CONT)、去神经支配诱导萎缩组(DEN)和DEN+B-SES电刺激组(DEN+ES)。治疗7天后,与CON组相比,DEN组和DEN+ES组的TA和GAS肌肉湿重(每组n=8-11)和肌纤维横截面积(CSA,每组n=6)均降低。DEN+ES组的肌肉重量和CSA显著高于DEN组。尽管RNA测序和通路分析表明线粒体生物合成是这一现象中的关键事件,但线粒体含量并无差异。相反,DEN+ES组的核糖体RNA 28S和18S(n=6)水平高于DEN组,尽管RNA测序显示电刺激会减少核糖体生物合成途径。肌肉蛋白水解分子atrogin-1和MuRF1的mRNA水平在DEN组显著高于CONT组。然而,它们在DEN+ES组中的抑制程度比DEN组更大。总之,使用腰带电极对双踝关节进行强直电刺激可有效减轻多个肌肉群的去神经支配诱导萎缩。此外,核糖体生物合成在这一现象中起着至关重要的作用。