Neuromuscular activity impairs axonal sprouting in partially denervated muscles by inhibiting bridge formation of perisynaptic Schwann cells

Abstract

Following partial denervation of rat hindlimb muscle, terminal Schwann cells extend processes from denervated endplates to induce and guide sprouting from the remaining intact axons. Increased neuromuscular activity significantly reduces motor unit enlargement and sprouting during the acute phase of sprouting. These findings led to the hypothesis that increased neuromuscular activity perturbs formation of Schwann cell bridges and thereby reduces sprouting. Adult rat tibialis anterior (TA) muscles were extensively denervated by avulsion of L4 spinal root and were immediately subjected to normal caged activity or running exercise (8 h daily) for 3, 7, 14, 21, and 28 days. Combined silver/cholinesterase histochemical staining revealed that the progressive reinnervation of denervated endplates by sprouts over a 1 month period in the extensively partially denervated TA muscles was completely abolished by increased neuromuscular activity. Immunohistochemical staining and triple immunofluorescence revealed that the increased neuromuscular activity did not perturb the production of Schwann cell processes, but prevented bridging between Schwann cell processes at innervated and denervated endplates. Our findings suggest that failure of Schwann cell processes to bridge between endplates accounts, at least in part, for the inhibitory effect of increased neuromuscular activity on sprouting.

Use of Neuromuscular Electrical Stimulation in the Treatment of Neonatal Brachial Plexus Palsy: A Literature Review

“…A major contributing factor may be the scarcity of human clinical studies involving NMES. Limitations of NMES suggested by neurophysiological studies and the controversy regarding its effectiveness from animal studies have possibly tempered impetus for further clinical evaluation in humans (Al-Majed et al, 2000;Tam & Gordon, 2003). One limitation of NMES suggested by neurophysiological studies is the manner in which motor units are activated during electrical stimulation.…”

Exercício imediato versus tardio na regeneração do nervo isquiático de ratos após axoniotmese: análise histomorfométrica e funcional

“…However, there are reports that the increased neuromuscular activity provoked by the running exercise on the wheel for eight hours a day, during the acute phase of the injury, inhibits axon budding in the denervated muscle 22,23 . It is possible that, in those studies, the impairment of reinnervation was due to the duration of the exercise, thereby differing from the results of the present study, in which the exercise lasted for 30 minutes each day.…”

Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice

“…Preterminal-and terminal Schwann cells serve as a growth substrate for the nodal sprouts, which guide them to the original endplates of denervated muscle fibers Thompson, 1995b,Koirala et al, 2000). In addition, tSC processes extending from denervated endplates contact intact nerve terminals, forming 'tSC bridges' that induce and guide terminal sprouts to denervated endplates (Son and Thompson, 1995a,Love et al, 2003,Tam and Gordon, 2003b. To test if terminal sprouting indeed cannot be elicited in CNTF−/− muscles and if an abnormal response of tSCs correlates with the sprouting defect, we transected L4 spinal roots and studied EDL muscles that were extensively denervated by the procedure (cf., Albani et al, 1988,Tam et al, 2001; see Methods).…”

“…Indeed, tSCs become reactive in response to paralysis or denervation (Reynolds and Woolf, 1992), and extend processes that appear to induce and guide terminal sprouts from innervated-to denervated muscle fibers (Son and Thompson, 1995a,Ko and Chen, 1996,Lubischer and Thompson, 1999,O'Malley et al, 1999,Love et al, 2003,Tam and Gordon, 2003b. Schwann cells are also the only cells in the peripheral nervous system that are known to express CNTF (Stockli et al, 1989,Friedman et al, 1992,Rende et al, 1992,Sendtner et al, 1992.…”