Abnormal response of distal Schwann cells to denervation in a mouse model of motor neuron disease

• Type of Material: Article
• Authors: Dario I. Carrasco, Emory University; Ben A. Bahr, University of North Carolina-Pembroke; Kevin L. Seburn, The Jackson Laboratory; Martin Pinter, Emory University
• Language: English
• Date: 2016-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2016.02.002
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 278
• Start Page: 116
• End Page: 126
• Grant/Funding Information: The Robert P. Apkarian Integrated Electron Microscopy Core of Emory University is supported by NIH grant S10RR025679.; This work was supported by NIH grants NS31621 and NS074231.
• Keywords: RAT NEUROMUSCULAR-JUNCTIONS; ALS; WALLERIAN DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; MICE; IN-VIVO; Denervation cell death; Motor neuron disease; Neurodegeneration; Life Sciences & Biomedicine; SCIATIC-NERVE; Science & Technology; Schwann cell; Motor terminal; Neurosciences; GLIAL-CELLS; Neurosciences & Neurology; GROWTH-FACTOR; NERVE DEGENERATION
• Research Categories: Biology, Neuroscience; Health Sciences, General

Abstract

In several animal models of motor neuron disease, degeneration begins in the periphery. Clarifying the possible role of Schwann cells remains a priority. We recently showed that terminal Schwann cells (TSCs) exhibit abnormalities in postnatal mice that express mutations of the SOD1 enzyme found in inherited human motor neuron disease. TSC abnormalities appeared before disease-related denervation commenced and the extent of TSC abnormality at P30 correlated with the extent of subsequent denervation. Denervated neuromuscular junctions (NMJs) were also observed that lacked any labeling for TSCs. This suggested that SOD1 TSCs may respond differently than wildtype TSCs to denervation which remain at denervated NMJs for several months. In the present study, the response of SOD1 TSCs to experimental denervation was examined. At P30 and P60, SC-specific S100 labeling was quickly lost from SOD1 NMJs and from preterminal regions. Evidence indicates that this loss eventually becomes complete at most SOD1 NMJs before reinnervation occurs. The loss of labeling was not specific for S100 and did not depend on loss of activity. Although some post-denervation labeling loss occurred at wildtype NMJs, this loss was never complete. Soon after denervation, large cells appeared near SOD1 NMJ bands which colabeled for SC markers as well as for activated caspase-suggesting that distal SOD1 SCs may experience cell death following denervation. Denervated SOD1 NMJs viewed 7 days after denervation with the electron microscope confirmed the absence of TSCs overlying endplates. These observations demonstrate that SOD1 TSCs and distal SCs respond abnormally to denervation. This behavior can be expected to hinder reinnervation and raises further questions concerning the ability of SOD1 TSCs to support normal functioning of motor terminals.