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Nat Commun. 2019 Apr 1;10(1):1467. doi: 10.1038/s41467-019-09385-6.

NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.

Author information

1
Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103, Leipzig, Germany. robert.fledrich@medizin.uni-leipzig.de.
2
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany. robert.fledrich@medizin.uni-leipzig.de.
3
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany.
4
Department of Neuropathology, University Hospital Leipzig, Liebigstr. 26, 04103, Leipzig, Germany.
5
Department of Clinical Neurophysiology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
6
Center for Research in Biotechnology (CIB), Costa Rican Institute of Technology (TEC), Cartago, Costa Rica.
7
Department of Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Str. 1, 30625, Hanover, Germany.
8
Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103, Leipzig, Germany.
9
Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
10
Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
11
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany. schwab.markus@mh-hannover.de.
12
Department of Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Str. 1, 30625, Hanover, Germany. schwab.markus@mh-hannover.de.
13
Center for Systems Neuroscience (ZSN), Bünteweg 2, 30559, Hanover, Germany. schwab.markus@mh-hannover.de.
14
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany. nave@em.mpg.de.
15
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany. ruth.stassart@medizin.uni-leipzig.de.
16
Department of Neuropathology, University Hospital Leipzig, Liebigstr. 26, 04103, Leipzig, Germany. ruth.stassart@medizin.uni-leipzig.de.

Abstract

In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental.

PMID:
30931926
PMCID:
PMC6443727
DOI:
10.1038/s41467-019-09385-6
[Indexed for MEDLINE]
Free PMC Article

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