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GABA-B1 Receptor-Null Schwann Cells Exhibit Compromised In Vitro Myelination

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Abstract

GABA-B receptors are important for Schwann cell (SC) commitment to a non-myelinating phenotype during development. However, the P0-GABA-B1fl/fl conditional knockout mice, lacking the GABA-B1 receptor specifically in SCs, also presented axon modifications, suggesting SC non-autonomous effects through the neuronal compartment. In this in vitro study, we evaluated whether the specific deletion of the GABA-B1 receptor in SCs may induce autonomous or non-autonomous cross-changes in sensory dorsal root ganglia (DRG) neurons. To this end, we performed an in vitro biomolecular and transcriptomic analysis of SC and DRG neuron primary cultures from P0-GABA-B1fl/fl mice. We found that cells from conditional P0-GABA-B1fl/fl mice exhibited proliferative, migratory and myelinating alterations. Moreover, we found transcriptomic changes in novel molecules that are involved in peripheral neuron–SC interaction.

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Acknowledgements

The authors are grateful to Astrid Williams for proofreading and Marinella Ballabio for technical support.

Funding

This work was supported by a grant from MIUR ‘Progetto Eccellenza’ and institutional grant from Università degli Studi di Milano (to V.M.); by grants from the Ministry of Economy and Competitiveness, Spain, MINECO BFU 2016-7798-P; and from Diputación Foral de Gipuzkoa, Spain DFG15/15 and DFG141/16 (to M.J.A.-B.).

Author information

Authors and Affiliations

  1. Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

    Alessandro Faroni

  2. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy

    Simona Melfi, Luca Franco Castelnovo, Veronica Bonalume, Deborah Colleoni, Paolo Magni & Valerio Magnaghi

  3. Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain

    Marcos J. Araúzo-Bravo

  4. Ikerbasque, Basque Foundation for Science, Bilbao, Spain

    Marcos J. Araúzo-Bravo

  5. Institute of Biomedical Technologies, National Research Council, Milan, Italy

    Rolland Reinbold

Authors
  1. Alessandro Faroni
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  2. Simona Melfi
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  3. Luca Franco Castelnovo
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  4. Veronica Bonalume
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  9. Valerio Magnaghi
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Contributions

A.F. performed animal crossing, genotyping and culture set-up; he also performed IIC; S.M. performed cell biology experiments (proliferation, migration, etc.); V.B. and D.C. set up the co-culture experiments; L.F.C. performed GABA-A qRT-PCRs; P.M. participated in the transcriptomic analysis; M.J.A-B. and R.R. performed transcriptomic in silico analysis and statistics; V.M. supervised all experiments and wrote the manuscript with A.F.

Corresponding author

Correspondence to Valerio Magnaghi.

Ethics declarations

All animal experiments were conducted in accordance with the European Communities Council Directive (2010/63) and were approved by the local ethical committee of the University of Milan.

Conflict of Interest

The authors have no other relevant affiliations or financial involvements with any organisation or entity with a financial interest in or financial conflict with the subjects discussed in the manuscript.

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Faroni, A., Melfi, S., Castelnovo, L.F. et al. GABA-B1 Receptor-Null Schwann Cells Exhibit Compromised In Vitro Myelination. Mol Neurobiol 56, 1461–1474 (2019). https://doi.org/10.1007/s12035-018-1158-x

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