Adaptive and maladaptive motor axonal sprouting in aging and motoneuron disease

Abstract Motor unit (MU) enlargement by sprouting is an important compensatory mechanism for loss of functional MUs during normal aging and neuromuscular disease. Perisynaptic Schwann cells at neuromuscular junctions extend processes that bridge between denervated and reinnervated endplates, and guide axonal sprouts to reinnervate the denervated endplates. In a rat model of partial denervation, high levels of daily neuromuscular activity have been shown to inhibit the outgrowth of sprouts by preventing Schwann cell bridging. In this review, we consider (1) the relative roles of increasing levels of oxidative stress and neuromuscular activity to the destabilization of neuromuscular junctions with ageand disease, and (2) how a progressive increase in the neuromuscular activity of declining numbers of functional MUs contributes to the progressive failure of adaptive sprouting and, in turn, to the progressive muscle weakness in the motoneuron diseases of post-polio syndrome and amyotrophic lateral sclerosis. ...