Clinical Relevance of Terminal Schwann Cells: An Overlooked Component of the Neuromuscular Junction

Overview

Journal J Neurosci Res

Specialty Neurology

Date 2018 Mar 15

PMID 29536564

Citations 39

Authors

Katherine B Santosa

Alexandra M Keane

Albina Jablonka-Shariff

Bianca Vannucci

Alison K Snyder-Warwick

Affiliations

Soon will be listed here.

Abstract

The terminal Schwann cell (tSC), a type of nonmyelinating Schwann cell, is a significant yet relatively understudied component of the neuromuscular junction. In addition to reviewing the role tSCs play on formation, maintenance, and remodeling of the synapse, we review studies that implicate tSCs in neuromuscular diseases including spinal muscular atrophy, Miller-Fisher syndrome, and amyotrophic lateral sclerosis, among others. We also discuss the importance of these cells on degeneration and regeneration after nerve injury. Knowledge of tSC biology may improve our understanding of disease pathogenesis and help us identify new and innovative therapeutic strategies for the many patients who suffer from neuromuscular disorders and nerve injuries.

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References

Robitaille R . Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. J Neurosci. 1995; 15(11):7121-31. PMC: 6578096. View

Feng Z, Ko C . The role of glial cells in the formation and maintenance of the neuromuscular junction. Ann N Y Acad Sci. 2008; 1132:19-28. DOI: 10.1196/annals.1405.016. View

Wigston D . Remodeling of neuromuscular junctions in adult mouse soleus. J Neurosci. 1989; 9(2):639-47. PMC: 6569784. View

Duregotti E, Negro S, Scorzeto M, Zornetta I, Dickinson B, Chang C . Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells. Proc Natl Acad Sci U S A. 2015; 112(5):E497-505. PMC: 4321248. DOI: 10.1073/pnas.1417108112. View

Reddy L, Koirala S, Sugiura Y, Herrera A, Ko C . Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo. Neuron. 2003; 40(3):563-80. DOI: 10.1016/s0896-6273(03)00682-2. View

DAmico A, Mercuri E, Tiziano F, Bertini E . Spinal muscular atrophy. Orphanet J Rare Dis. 2011; 6:71. PMC: 3231874. DOI: 10.1186/1750-1172-6-71. View

Portincasa A, Gozzo G, Parisi D, Annacontini L, Campanale A, Basso G . Microsurgical treatment of injury to peripheral nerves in upper and lower limbs: a critical review of the last 8 years. Microsurgery. 2007; 27(5):455-62. DOI: 10.1002/micr.20382. View

Chiba A, Kusunoki S, Shimizu T, Kanazawa I . Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol. 1992; 31(6):677-9. DOI: 10.1002/ana.410310619. View

Neve A, Trub J, Saxena S, Schumperli D . Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice. Mol Cell Neurosci. 2015; 70:30-41. DOI: 10.1016/j.mcn.2015.11.007. View

10.

Darabid H, Perez-Gonzalez A, Robitaille R . Neuromuscular synaptogenesis: coordinating partners with multiple functions. Nat Rev Neurosci. 2014; 15(11):703-18. View

11.

Trachtenberg J, Thompson W . Nerve terminal withdrawal from rat neuromuscular junctions induced by neuregulin and Schwann cells. J Neurosci. 1997; 17(16):6243-55. PMC: 6568340. View

12.

Nicole S, Chaouch A, Torbergsen T, Bauche S, De Bruyckere E, Fontenille M . Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. Brain. 2014; 137(Pt 9):2429-43. DOI: 10.1093/brain/awu160. View

13.

Todd K, Darabid H, Robitaille R . Perisynaptic glia discriminate patterns of motor nerve activity and influence plasticity at the neuromuscular junction. J Neurosci. 2010; 30(35):11870-82. PMC: 6633406. DOI: 10.1523/JNEUROSCI.3165-10.2010. View

14.

Bourque M, Robitaille R . Endogenous peptidergic modulation of perisynaptic Schwann cells at the frog neuromuscular junction. J Physiol. 1998; 512 ( Pt 1):197-209. PMC: 2231189. DOI: 10.1111/j.1469-7793.1998.197bf.x. View

15.

Halstead S, Humphreys P, Zitman F, Hamer J, Plomp J, Willison H . C5 inhibitor rEV576 protects against neural injury in an in vitro mouse model of Miller Fisher syndrome. J Peripher Nerv Syst. 2008; 13(3):228-35. DOI: 10.1111/j.1529-8027.2008.00181.x. View

16.

Woldeyesus M, Britsch S, Riethmacher D, Xu L, Harvey R, Caroni P . Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development. Genes Dev. 1999; 13(19):2538-48. PMC: 317072. DOI: 10.1101/gad.13.19.2538. View

17.

Casano A, Peri F . Microglia: multitasking specialists of the brain. Dev Cell. 2015; 32(4):469-77. DOI: 10.1016/j.devcel.2015.01.018. View

18.

OHanlon G, Plomp J, Chakrabarti M, Morrison I, Wagner E, Goodyear C . Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal. Brain. 2001; 124(Pt 5):893-906. DOI: 10.1093/brain/124.5.893. View

19.

Kang H, Tian L, Mikesh M, Lichtman J, Thompson W . Terminal Schwann cells participate in neuromuscular synapse remodeling during reinnervation following nerve injury. J Neurosci. 2014; 34(18):6323-33. PMC: 4004816. DOI: 10.1523/JNEUROSCI.4673-13.2014. View

20.

Bruneteau G, Bauche S, Gonzalez de Aguilar J, Brochier G, Mandjee N, Tanguy M . Endplate denervation correlates with Nogo-A muscle expression in amyotrophic lateral sclerosis patients. Ann Clin Transl Neurol. 2015; 2(4):362-72. PMC: 4402082. DOI: 10.1002/acn3.179. View