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Author Notes:

Corresponding author: Martin J. Pinter, Department of Physiology, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, Email: mpinter@emory.edu

The authors wish to thank Drs. Mark Rich and Greg Cox for helpful discussions.

The authors declare no competing financial interests.

Subjects:

Research Funding:

This work was supported by NIH grant NS074231.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Motor neuron disease
  • Terminal Schwann cell
  • Neurodegeneration
  • Motor terminal
  • Denervation
  • Neuromuscular junction
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • MAMMALIAN NEUROMUSCULAR-JUNCTION
  • MOTOR-NEURON DEGENERATION
  • GLIAL-CELLS
  • MOUSE MODEL
  • SOD1(G93A) MICE
  • IN-VIVO
  • SYNAPTIC COMPETITION
  • BOTULINUM TOXIN
  • TRANSGENIC MICE

Altered terminal Schwann cell morphology precedes denervation in SOD1 mice

Tools:

Journal Title:

Experimental Neurology

Volume:

Volume 275

Publisher:

, Pages 172-181

Type of Work:

Article | Post-print: After Peer Review

Abstract:

In mice that express SOD1 mutations found in human motor neuron disease, degeneration begins in the periphery for reasons that remain unknown. At the neuromuscular junction (NMJ), terminal Schwann cells (TSCs) have an intimate relationship with motor terminals and are believed to help maintain the integrity of the motor terminal. Recent evidence indicates that TSCs in some SOD1 mice exhibit abnormal functional properties, but other aspects of possible TSC involvement remain unknown. In this study, an analysis of TSC morphology and number was performed in relation to NMJ innervation status in mice which express the G93A SOD1 mutation. At P30, all NMJs of the fast medial gastrocnemius (MG) muscle were fully innervated by a single motor axon but 50% of NMJs lacked TSC cell bodies and were instead covered by the processes of Schwann cells with cell bodies located on the preterminal axons. NMJs in P30 slow soleus muscles were also fully innervated by single motor axons and only 5% of NMJs lacked a TSC cell body. At P60, about 25% of MG NMJs were denervated and lacked labeling for TSCs while about 60% of innervated NMJs lacked TSC cell bodies. In contrast, 96% of P60 soleus NMJs were innervated while 9% of innervated NMJs lacked TSC cell bodies. The pattern of TSC abnormalities found at P30 thus correlates with the pattern of denervation found at P60. Evidence from mice that express the G85R SOD1 mutation indicate that TSC abnormalities are not unique for mice that express G93A SOD1 mutations. These results add to an emerging understanding that TSCs may play a role in motor terminal degeneration and denervation in animal models of motor neuron disease.

Copyright information:

© 2015 Elsevier Inc.

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