title: Abnormal response of distal Schwann cells to denervation in a mouse model of motor neuron disease.
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-3 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.
authors: Department of Physiology, Emory University, Atlanta, GA, USA.
authors: Dario I
authors: DI
authors: Carrasco
authors: Biotechnology Research and Training Center, University of North Carolina at Pembroke, Pembroke, NC, USA.
authors: Ben A
authors: BA
authors: Bahr
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Kevin L
authors: KL
authors: Seburn
authors: Department of Physiology, Emory University, Atlanta, GA, USA. Electronic address: mpinter@emory.edu.
authors: Martin J
authors: MJ
authors: Pinter
mesh_terms: D000367:Age Factors; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology*; D009121:Muscle Denervation / Q000379:methods; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology*; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D020800:Receptor, Nerve Growth Factor; D011950:Receptors, Cholinergic; D009418:S100 Proteins; C036763:monocyte-macrophage differentiation antigen; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Denervation cell death; Motor neuron disease; Motor terminal; Neurodegeneration; Schwann cell