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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Loss of Schwann cell plasticity in chronic inflammatory demyelinating polyneuropathy (CIDP)

Authors: Abhijeet R. Joshi, Laura Holtmann, Ilja Bobylev, Christian Schneider, Christian Ritter, Joachim Weis, Helmar C. Lehmann

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

Chronic inflammatory demyelinating polyneuropathy (CIDP) is often associated with chronic disability, which can be accounted to incomplete regeneration of injured axons. We hypothesized that Schwann cell support for regenerating axons may be altered in CIDP, which may account for the poor clinical recovery seen in many patients.

Methods

We exposed human and rodent Schwann cells to sera from CIDP patients and controls. In a model of chronic nerve denervation, we transplanted these conditioned Schwann cells intraneurally and assessed their capacity to support axonal regeneration by electrophysiology and morphometry.

Results

CIDP-conditioned Schwann cells were less growth supportive for regenerating axons as compared to Schwann cells exposed to control sera. The loss of Schwann cell support was associated with lower levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CIDP sera and correlated with altered expression of c-Jun and p57kip2 in Schwann cells. The inactivation of these regulatory factors resulted in an altered expression of neurotrophins including BDNF, GDNF, and NGF in CIDP-conditioned Schwann cells in vitro.

Conclusions

Our study provides evidence that pro-regenerative functions of Schwann cells are affected in CIDP. It thereby offers a possible explanation for the clinical observation that in many CIDP patients recovery is incomplete despite sufficient immunosuppressive treatment.
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Literature
1.
2.
Mathys C, Aissa J, Hoerste GM, Meyer G, Reichelt DC, Antoch G, Turowski B, Hartung H-P, Sheikh KA, Lehmann HC. Peripheral neuropathy: assessment of proximal nerve integrity by diffusion tensor imaging. Muscle Nerve. 2013;48:889–96.CrossRefPubMed
3.
Simmons Z, Albers J, Bromberg M, Feldman E. Long-term follow-up of patients with chronic inflammatory demyelinating polyradiculoneuropathy, without and with monoclonal gammopathy. Brain. 1995;118(Pt 2):359–68.CrossRefPubMed
4.
Köller H, Kieseier BC, Jander S, Hartung H-P. Chronic inflammatory demyelinating polyneuropathy. N Engl J Med. 2005;352:1343–56.CrossRefPubMed
5.
Iijima M, Yamamoto M, Hirayama M, Tanaka F, Katsuno M, Mori K, Koike H, Hattori N, Arimura K, Nakagawa M. Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. Neurology. 2005;64:1471–5.CrossRefPubMed
6.
Joshi AR, Bobylev I, Zhang G, Sheikh KA, Lehmann HC. Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves. Exp Neurol. 2015;263:28–38.CrossRefPubMed
7.
Arthur-Farraj PJ, Latouche M, Wilton DK, Quintes S, Chabrol E, Banerjee A, Woodhoo A, Jenkins B, Rahman M, Turmaine M. c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron. 2012;75:633–47.CrossRefPubMedPubMedCentral
8.
Allodi I, Udina E, Navarro X. Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol. 2012;98:16–37.CrossRefPubMed
9.
Jessen KR, Mirsky R. Negative regulation of myelination: relevance for development, injury, and demyelinating disease. Glia. 2008;56:1552–65.CrossRefPubMed
10.
Heinen A, Kremer D, Gottle P, Kruse F, Hasse B, Lehmann H, Hartung HP, Küry P. The cyclin-dependent kinase inhibitor p57kip2 is a negative regulator of Schwann cell differentiation and in vitro myelination. Proc Natl Acad Sci U S A. 2008;105:8748–53.CrossRefPubMedPubMedCentral
11.
Heinen A, Lehmann HC, Küry P. Negative regulators of Schwann cell differentiation: novel targets for peripheral nerve therapies? J Clin Immunol. 2013;33:18–26.CrossRef
12.
Mirsky R, Jessen KR. Schwann cell development, differentiation and myelination. Curr Opin Neurobiol. 1996;6:89–96.CrossRefPubMed
13.
Van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, Koski CL, Leger JM, Nobile-Orazio E, Pollard J. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society: first revision. Eur J Neurol. 2010;17:356–63.CrossRefPubMed
14.
Brockes JP, Fields KL, Raff MC. Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Res. 1979;165:105–18.CrossRefPubMed
15.
Ritter C, Bobylev I, Lehmann HC. Chronic inflammatory demyelinating polyneuropathy (CIDP): change of serum IgG dimer levels during treatment with intravenous immunoglobulins. J Neuroinflammation. 2015;12:1.CrossRef
16.
Lehmann HC, Lopez PHH, Zhang G, Ngyuen T, Zhang J, Kieseier BC, Mori S, Sheikh KA. Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model. J Neurosci. 2007;27:27–34.CrossRefPubMed
17.
Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci. 1995;15:3886–95.PubMed
18.
Heine W, Conant K, Griffin JW, Hoke A. Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp Neurol. 2004;189:231–40.CrossRefPubMed
19.
Chernousov MA, Rothblum K, Stahl RC, Evans A, Prentiss L, Carey DJ. Glypican-1 and alpha-4 (V) collagen are required for Schwann cell myelination. J Neurosci. 2006;26:508–17.CrossRefPubMed
20.
Gnavi S, Fornasari BE, Tonda-Turo C, Laurano R, Zanetti M, Ciardelli G, Geuna S. The effect of electrospun gelatin fibers alignment on Schwann cell and axon behavior and organization in the perspective of artificial nerve design. Int J Mol Sci. 2015;16:12925–42.CrossRefPubMedPubMedCentral
21.
Lopez-Fagundo C, Bar-Kochba E, Livi LL, Hoffman-Kim D, Franck C. Three-dimensional traction forces of Schwann cells on compliant substrates. J R Soc Interface. 2015;11:20140247.CrossRef
22.
Küry P, Greiner-Petter R, Cornely C, Jorgens T, Muller HW. Mammalian achaete scute homolog 2 is expressed in the adult sciatic nerve and regulates the expression of Krox24, Mob-1, CXCR4, and p57kip2 in Schwann cells. J Neurosci. 2002;22:7586–95.PubMed
23.
Fontana X, Hristova M, Da Costa C, Patodia S, Thei L, Makwana M, Spencer-Dene B, Latouche M, Mirsky R, Jessen KR. c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling. J Cell Biol. 2012;198:127–41.CrossRefPubMedPubMedCentral
24.
Rajabally YA, Nicolas G, Pieret F, Bouche P, Van den Bergh PYK. Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study. J Neurol Neurosurg Psychiatry. 2009;80:1364–8.CrossRefPubMed
25.
Harbo T, Andersen H, Jakobsen J. Length-dependent weakness and electrophysiological signs of secondary axonal loss in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. 2008;38:1036–45.CrossRefPubMed
26.
Franzen R, Bouhy D, Schoenen J. Nervous system injury: focus on the inflammatory cytokine 'granulocyte-macrophage colony stimulating factor'. Neurosci Lett. 2004;361:76–8.CrossRefPubMed
27.
Sainaghi PP, Collimedaglia L, Alciato F, Leone MA, Naldi P, Molinari R, Monaco F, Avanzi GC. The expression pattern of inflammatory mediators in cerebrospinal fluid differentiates Guillain-Barre syndrome from chronic inflammatory demyelinating polyneuropathy. Cytokine. 2010;51:138–43.CrossRefPubMed
28.
Reichert F, Saada A, Rotshenker S. The cytokine network of Wallerian degeneration: IL-10 and GM-CSF. Eur J Neurosci. 1998;10:2707–13.CrossRefPubMed
29.
Mirski R, Reichert F, Klar A, Rotshenker S. Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons. J Neuroimmunol. 2003;140:88–96.CrossRefPubMed
30.
Rotshenker S: Wallerian degeneration. In: Encyclopedia of Pain. Springer; 2013: 4251-4258
31.
Adunyah SE, Unlap TM, Wagner F, Kraft AS. Regulation of c-jun expression and AP-1 enhancer activity by granulocyte-macrophage colony-stimulating factor. J Biol Chem. 1991;266:5670–5.PubMed
32.
Konishi Y, Chui D, Hirose H, Kunishita T, Tabira T. Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res. 1993;609:29–35.CrossRefPubMed
33.
Parkinson DB, Bhaskaran A, Arthur-Farraj P, Noon LA, Woodhoo A, Lloyd AC, Feltri ML, Wrabetz L, Behrens A, Mirsky R. c-Jun is a negative regulator of myelination. J Cell Biol. 2008;181:625–37.CrossRefPubMedPubMedCentral
34.
Hutton EJ, Carty L, Laura M, Houlden H, Lunn M, Brandner S, Mirsky R, Jessen K, Reilly MM. c-Jun expression in human neuropathies: a pilot study. J Peripher Nerv Syst. 2011;16:295–303.CrossRefPubMed
35.
Boyd JG, Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol. 2003;183:610–9.CrossRefPubMed
36.
Zhang JY, Luo XG, Xian CJ, Liu ZH, Zhou XF. Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci. 2000;12:4171–80.PubMed
37.
Yin Q, Kemp GJ, Frostick SP. Neurotrophins, neurones and peripheral nerve regeneration. J Hand Surg Eur Vol. 1998;23:433–7.CrossRef
38.
Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience. 1997;76:1153–8.CrossRefPubMed
39.
Huang L, Quan X, Liu Z, Ma T, Wu Y, Ge J, Zhu S, Yang Y, Liu L, Sun Z. c-Jun gene-modified Schwann cells: upregulating multiple neurotrophic factors and promoting neurite outgrowth. Tissue Eng Part A. 2015;21:1409–21.CrossRefPubMedPubMedCentral
40.
Sulaiman OAR, Gordon T. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size. Glia. 2000;32:234–46.CrossRefPubMed
Metadata
Title
Loss of Schwann cell plasticity in chronic inflammatory demyelinating polyneuropathy (CIDP)
Authors
Abhijeet R. Joshi
Laura Holtmann
Ilja Bobylev
Christian Schneider
Christian Ritter
Joachim Weis
Helmar C. Lehmann
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0711-7

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