title: Acupuncture plus low-frequency electrical stimulation (Acu-LFES) attenuates denervation-induced muscle atrophy.
abstract: Muscle wasting occurs in a variety of clinical situations, including denervation. There is no effective pharmacological treatment for muscle wasting. In this study, we used a tibial nerve denervation model to test acupuncture plus low-frequency electric stimulation (Acu-LFES) as a therapeutic strategy for muscle atrophy. Acupuncture needles were connected to an SDZ-II electronic acupuncture device delivering pulses at 20 Hz and 1 mA; the treatment was 15 min daily for 2 wk. Acu-LFES prevented soleus and plantaris muscle weight loss and increased muscle cross-sectional area in denervated mice. The abundances of Pax7, MyoD, myogenin, and embryonic myosin heavy chain were significantly increased by Acu-LFES in both normal and denervated muscle. The number of central nuclei was increased in Acu-LFES-treated muscle fibers. Phosphorylation of Akt was downregulated by denervation leading to a decline in muscle mass; however, Acu-LFES prevented the denervation-induced decline largely by upregulation of the IGF-1 signaling pathway. Acu-LFES reduced the abundance of muscle catabolic proteins forkhead O transcription factor and myostatin, contributing to the attenuated muscle atrophy. Acu-LFES stimulated the expression of macrophage markers (F4/80, IL-1b, and arginase-1) and inflammatory cytokines (IL-6, IFNγ, and TNFα) in normal and denervated muscle. Acu-LFES also stimulated production of the muscle-specific microRNAs miR-1 and miR-206. We conclude that Acu-LFES is effective in counteracting denervation-induced skeletal muscle atrophy and increasing muscle regeneration. Upregulation of IGF-1, downregulation of myostatin, and alteration of microRNAs contribute to the attenuation of muscle atrophy in denervated mice.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Su
authors.affiliation: Acumox and Tuina Research Section, College of Acumox and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Li
authors.initials: L
authors.lastname: Hu
authors.affiliation: Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas; and.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Faten
authors.initials: F
authors.lastname: Hassounah
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia xwang03@emory.edu.
authors.forename: Haidong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Xiaonan H
authors.initials: XH
authors.lastname: Wang
mesh_terms: D015670:Acupuncture Therapy / Q000379:methods*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D009121:Muscle Denervation / Q000009:adverse effects*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism / Q000628:therapy*; D018995:Myosin Heavy Chains / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism; D009339:Needles; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013979:Tibial Nerve / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D009124:Muscle Proteins; D055435:Myostatin; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D018995:Myosin Heavy Chains
keywords: Akt; FoxO; IGF-1; cytokines; macrophage; myostatin