Neuron‐specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD knockout mice (1153.3)

Abstract

Deletion of CuZnSOD in Sod1‐/‐ mice leads to accelerated loss of muscle mass and force during aging. To determine the role of motor neurons in the muscle declines, we generated a transgenic Sod1‐/‐ mouse in which CuZnSOD was expressed under control of a synapsin 1 promoter (SynTgSod1‐/‐ mice). These “rescue” mice expressed CuZnSOD in brain, spinal cord, and peripheral nerves, but not other tissues. Sciatic nerve CuZnSOD content in SynTgSod1‐/‐ mice was ~20% that of control mice, but no reduction in muscle mass or maximum isometric force was observed for the rescue mice compared with controls at 15 months, whereas muscles of age‐matched Sod1‐/‐ mice displayed 30‐35% reductions in mass and force. Increased oxidative damage and adaptations in stress responses observed in muscles of Sod1‐/‐ mice were absent in SynTgSod1‐/‐ mice and accelerated degeneration of neuromuscular junction (NMJ) structure occurred in Sod1‐/‐ mice but not SynTgSod1‐/‐ mice. Our data demonstrate that CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1‐/‐ mice and suggest that redox homeostasis in motor neurons plays a key role in the initiation of sarcopenia during aging.Grant Funding Source: Supported by the US National Institute on Aging (Grant No: AG‐020591)