Terminal Schwann Cells Participate in Neuromuscular Synapse Remodeling during Reinnervation following Nerve Injury

Abstract

Schwann cells (SCs) at neuromuscular junctions (NMJs) play active roles in synaptic homeostasis and repair. We have studied how SCs contribute to reinnervation of NMJs using vital imaging of mice whose motor axons and SCs are transgenically labeled with different colors of fluorescent proteins. Motor axons most commonly regenerate to the original synaptic site by following SC-filled endoneurial tubes. During the period of denervation, SCs at the NMJ extend elaborate processes from the junction, as shown previously, but they also retract some processes from territory they previously occupied within the endplate. The degree of this retraction depends on the length of the period of denervation. We show that the topology of the remaining SC processes influences the branching pattern of regenerating axon terminals and the redistribution of acetylcholine receptors (AChRs). Upon arriving at the junction, regenerating axons follow existing SC processes within the old synaptic site. Some of the AChR loss that follows denervation is correlated with failure of portions of the old synaptic site that lack SC coverage to be reinnervated. New AChR clustering is also induced by axon terminals that follow SC processes extended during denervation. These observations show that SCs participate actively in the remodeling of neuromuscular synapses following nerve injury by their guidance of axonal reinnervation.

Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS

“…Perisynaptic Schwann cells are glial cells at the NMJs that ensure the synapse stability, maintenance, and repair during damage or denervation (41). Perisynaptic Schwann cells respond to ALS-induced denervation with profound morphological and phenotypic changes (17), retracting processes from the NMJs while extending processes to other endplate areas (42). Therefore, we examined whether downregulation of mast cells in masitinib-treated rats was associated to preservation of perisynaptic Schwann cells in the EDL muscle, as analyzed by confocal microscopy followed by 3-D reconstructions.…”

Neuregulin/ErbB Signaling in Developmental Myelin Formation and Nerve Repair

“…Nrg1 also promotes the survival of terminal Schwann cells that envelop the neuromuscular junction, and these cells contribute to remodeling of the neuromuscular synapse after injury and to reinnervation of denervated synapses (Kang et al, 2014). The survival of terminal Schwann cells after neonatal denervation can be improved through Nrg1 administration, and they remain responsive to Nrg1 in adulthood (Trachtenberg and Thompson, 1996).…”

Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials

“…The Na ϩ current (I Na ) density in the calyx of Held was found to be low, and Na ϩ influx at the heminode was assumed to provide the current for full-height APs at release sites (Leao et al 2005). Although the vertebrate NMJ exhibits considerable variation in morphology across species and locations, a significant proportion of motor end plates are morphologically compact, with 2-4 orders of branching within a space of 20 ϫ 60 m (Kang et al 2014). Compact NMJ terminals are either not excitable or have low excitability (Brigant and Mallart 1982;Krzemien et al 2000).…”