Magnetic Stimulation Counteracts the Progression of Immobilization‐Induced Muscle Atrophy in Rats

ABSTRACT Background Physical exercise is recommended for sarcopenia prevention and treatment. Patients with frailty often show poor tolerance. To achieve universal availability, electrical stimulation of skeletal muscles has been devised, but concerns remain regarding efficacy and safety. Alternatively, magnetic stimulation could theoretically induce skeletal muscle contractions by remotely inducing electric fields, which may be a promising noninvasive approach. Our objective is to examine the efficacy and underlying mechanisms of magnetic stimulation against disuse muscle atrophy in a rat model of wire hindlimb immobilization. Methods Rats were divided into the following three groups: control (n = 5), those with spiral wire immobilization (SWI)‐induced hindlimb muscle atrophy (n = 6) and those with SWI undergoing magnetic stimulation (n = 5). Magnetic stimulation was set at 30 Hz, intensity 25%, 800 trains and 12 000 pulses/day for 5 days. Rats were evaluated for muscle strength and harvested soleus and gastrocnemius muscles for transcriptome and metabolome analysis. Results The body weight (144.8 ± 6.5 g vs. 175.2 ± 5.6 g) and the weight of the soleus (0.037 ± 0.01 g vs. 0.065 ± 0.01 g) and gastrocnemius muscles (0.599 ± 0.02 g vs. 0.966 ± 0.05 g) were lower in the SWI than the controls (p < 0.05). Intriguingly, the weight of gastrocnemius muscle (0.654 ± 0.024 g vs. 0.599 ± 0.01 g, p < 0.05) and maximal knee extension twitch torque (110.49 ± 8.57 mNm vs. 84.57 ± 6.61 mNm, p < 0.05) were greater in rats with SWI and magnetic stimulation than in rats with SWI alone. RNA‐seq identified 469 genes that were downregulated by SWI, 190 genes that were upregulated by magnetic stimulation. Metabolome profiling indicated altered glutathione metabolism in SWI muscles (−Log10(P‐value) = 3.2, −Log10(false discovery rate, FDR) = 1.6), whereas magnetic stimulation influenced purine metabolism (−Log10(P‐value) = 2.8, −Log10(FDR) = 0.9), partially supported by RNA‐seq differentially expressed gene list. In engineered human muscle tissues, treatment with 1 μM L‐alanosine, a purine metabolism inhibitor, negatively affected the maintenance of the electric pulse stimulation‐induced contractile function; twitch forces were 0.12 ± 0.09 mN with 0.69 ± 0.14 mN as control (p < 0.05) and tetanic forces were 0.28 ± 0.23 mN with 1.55 ± 0.33 mN as control (p < 0.05). Conclusions Magnetic stimulation counteracted the loss of weight and function of murine gastrocnemius muscle induced by immobilization and may have the potential to halt the progression of sarcopenia via alteration of the metabolic pathway in the muscle.