Loss of neuromuscular junction integrity and muscle atrophy in skeletal muscle disuse.

Physical inactivity (PI) is a major risk factor of chronic diseases. A major aspect of PI is loss of muscle mass and strength. The latter phenomenon significantly impacts daily life and represent a major issue for global health. Understandably, skeletal muscle itself has been the major focus of studies aimed at understanding the mechanisms underlying loss of mass and strength. Relatively lesser attention has been given to the contribution of alterations in somatomotor control, despite the fact that these changes can start very early and can occur at multiple levels, from the cortex down to the neuromuscular junction (NMJ). It is well known that exposure to chronic inactivity or immobilization causes a disproportionate loss of force compared to muscle mass, i.e. a loss of specific or intrinsic whole muscle force. The latter phenomenon may be partially explained by the loss of specific force of individual muscle fibres, but several other players are very likely to contribute to such detrimental phenomenon. Irrespective of the length of the disuse period, the loss of force is, in fact, more than two-fold greater than that of muscle size. It is very likely that somatomotor alterations may contribute to this loss in intrinsic muscle force. Here we review evidence that alterations of one component of somatomotor control, namely the neuromuscular junction, occur in disuse. We also discuss some of the novel players in NMJ stability (e.g., homer, bassoon, pannexin) and the importance of new established and emerging molecular markers of neurodegenerative processes in humans such as agrin, neural-cell adhesion molecule and light-chain neurofilaments.

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