In vivo Studies of Motor Nerve Re‐growth in Adult and Old Mice Following Contraction‐induced Injury

Abstract

Little is known about the changes in motor neurons that occur following contraction‐induced skeletal muscle injury and regeneration, a process that is defective in muscles of old rodents and may play a major role in the development of sarcopenia. The aim of this work was to examine structural changes in motor neurons and neuromuscular junctions (NMJs) following damaging lengthening contractions and whether this process is defective in muscles of old mice. Studies were undertaken in Thy1‐YFP transgenic mice that only express YFP in neuronal cells. One extensor digitorum longus (EDL) muscle of adult and old mice was subjected to a protocol of lengthening contractions. Structural changes in NMJs as well as the loss and regrowth of peripheral motor neurons were examined by fluorescence microscopy. Muscle fiber damage and regeneration was confirmed histologically. Three days after injury, muscles from adult and old mice showed widespread necrosis. By 28 days, muscles from adult mice appeared histologically normal, whereas muscles from old mice at 28 days following damage showed multiple small atrophic fibers and fibers with central nuclei. Major disruption of the NMJs was seen at 3 days following damage in both adult and old mice, followed by re‐innervation of the muscle that was completed by 28 days in adult mice (96% of the NMJs in EDL muscles from adult mice appeared to be normal with only 2% showing full denervation), but which remained sub‐optimal in muscles of old mice. Data indicate that muscle aging influences muscle regeneration, innervation and NMJ plasticity. Supported by Research into Ageing/AgeUK.