ArticlePloS one2014
The lack of CuZnSOD leads to impaired neurotransmitter release, neuromuscular junction destabilization and reduced muscle strength in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Effects of exercise on neuromuscular junction components across age: systematic review of animal experimental studies.BMC research notes · 2015Pooled it
- The role of resistance training and creatine supplementation on oxidative stress, antioxidant defense, muscle strength, and quality of life in older adults.Frontiers in public health · 2023Trial
- Effect of cysteine-rich whey protein (immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass in non-frail elderly subjects: a randomized, double-blind controlled study.The journal of nutrition, health & aging · 2015Trial
- Acute mitochondrial dysfunction impairs neuromuscular transmission and contractility in mouse diaphragm: the protective potential of 25-hydroxycholesterol.Journal of physiology and biochemistry · 2026Article
- Frequency-Dependent Mechanism of 24-Hydroxycholesterol-Mediated Modulation of Neurotransmitter Release at the Mouse Neuromuscular Junction: The Role of Reactive Oxygen Species.Neurochemical research · 2025Article
- Neurotoxic effects of acyclovir: impacts on oxidative stress, inflammation, and neurotransmitter dynamics in male Wistar rats.Metabolic brain disease · 2025Article
- Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria.Frontiers in physiology · 2025Review
- Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction.Physiological reports · 2024Review
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Older mice show decreased regeneration of neuromuscular junctions following lengthening contraction-induced injury.GeroScience · 2023Article
- Acylated Ghrelin Receptor Agonist HM01 Decreases Lean Body and Muscle Mass, but Unacylated Ghrelin Protects against Redox-Dependent Sarcopenia.Antioxidants (Basel, Switzerland) · 2022Article
- Saffron (Nutrients · 2022Review
- Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster.Molecular neurobiology · 2021Article
- Mouse models of sarcopenia: classification and evaluation.Journal of cachexia, sarcopenia and muscle · 2021Review
- Review
- Cancer cachexia in a mouse model of oxidative stress.Journal of cachexia, sarcopenia and muscle · 2020Article
- Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia.GeroScience · 2020Article
- Protective Effects of Hydrogen-Rich Water Against Cartilage Damage in a Rat Model of Osteoarthritis by Inhibiting Oxidative Stress, Matrix Catabolism, and Apoptosis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions.Frontiers in molecular neuroscience · 2020Review
- Using MRI to measure in vivo free radical production and perfusion dynamics in a mouse model of elevated oxidative stress and neurogenic atrophy.Redox biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated reactive oxygen species (ROS) production and ROS-dependent protein damage is a common observation in the pathogenesis of many muscle wasting disorders, including sarcopenia. However, the contribution of elevated ROS levels to -a breakdown in neuromuscular communication and muscle atrophy remains unknown. In this study, we examined a copper zinc superoxide dismutase [CuZnSOD (Sod1)] knockout mouse (Sod1-/-), a mouse model of elevated oxidative stress that exhibits accelerated loss of muscle mass, which recapitulates many phenotypes of sarcopenia as early as 5 months of age. We found that young adult Sod1-/- mice display a considerable reduction in hind limb skeletal muscle mass and strength when compared to age-matched wild-type mice. These changes are accompanied by gross alterations in neuromuscular junction (NMJ) morphology, including reduced occupancy of the motor endplates by axons, terminal sprouting and axon thinning and irregular swelling. Surprisingly however, the average density of acetylcholine receptors in endplates is preserved. Using in vivo electromyography and ex vivo electrophysiological studies of hind limb muscles in Sod1-/- mice, we found that motor axons innervating the extensor digitorum longus (EDL) and gastrocnemius muscles release fewer synaptic vesicles upon nerve stimulation. Recordings from individually identified EDL NMJs show that reductions in neurotransmitter release are apparent in the Sod1-/- mice even when endplates are close to fully innervated. However, electrophysiological properties, such as input resistance, resting membrane potential and spontaneous neurotransmitter release kinetics (but not frequency) are similar between EDL muscles of Sod1-/- and wild-type mice. Administration of the potassium channel blocker 3,4-diaminopyridine, which broadens the presynaptic action potential, improves both neurotransmitter release and muscle strength. Together, these results suggest that ROS-associated motor nerve terminal dysfunction is a contributor to the observed muscle changes in Sod1-/- mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.