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Demyelination induces transport of ribosome-containing vesicles from glia to axons: evidence from animal models and MS patient brains

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Abstract

Glial cells were previously proven capable of trafficking polyribosomes to injured axons. However, the occurrence of such transfer in the general pathological context, such as demyelination-related diseases, needs further evidence. Since this may be a yet unidentified universal contributor to axonal survival, we study putative glia–axonal ribosome transport in response to demyelination in animal models and patients in both peripheral and central nervous system. In the PNS we investigate whether demyelination in a rodent model has the potential to induce ribosome transfer. We also probe the glia–axonal ribosome supply by implantation of transgenic Schwann cells engineered to produce fluorescent ribosomes in the same demyelination model. We furthermore examine the presence of axonal ribosomes in mouse experimental autoimmune encephalomyelitis (EAE), a well-established model for multiple sclerosis (MS), and in human MS autopsy brain material. We provide evidence for increased axonal ribosome content in a pharmacologically demyelinated sciatic nerve, and demonstrate that at least part of these ribosomes originate in the transgenic Schwann cells. In the CNS one of the hallmarks of MS is demyelination, which is associated with severe disruption of oligodendrocyte–axon interaction. Here, we provide evidence that axons from spinal cords of EAE mice, and in the MS human brain contain an elevated amount of axonal ribosomes compared to controls. Our data provide evidence that increased axonal ribosome content in pathological axons is at least partly due to glia-to-axon transfer of ribosomes, and that demyelination in the PNS and in the CNS is one of the triggers capable to initiate this process.

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Acknowledgments

This research was supported by a collaborative grant from the MS Scientific Foundation Canada

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    Authors and Affiliations

    1. Hotchkiss Brain Institute and Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

      Antos Shakhbazau, Curtis Hay, Jean Kawasoe, V. Wee Yong & Jan van Minnen

    2. Department of Anatomy and Neurosciences, VU University Medical Centre, Neuroscience Campus Amsterdam, De Boelenlaan 1108, 1081 HV, Amsterdam, The Netherlands

      Geert J. Schenk, Roel Klaver & Jeroen J. G. Geurts

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    1. Antos Shakhbazau
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    Antos Shakhbazau and Geert J. Schenk have contributed equally to this article.

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    Glossary

    SC

    Schwann cells

    PNS

    Peripheral nervous system

    CNS

    Central nervous system

    EAE

    Experimental autoimmune encephalomyelitis

    EM

    Electron microscopy

    MS

    Multiple sclerosis

    eGFP

    Enhanced green fluorescent protein

    PBS

    Phosphate-buffered saline

    GA

    Glutaraldehyde

    PFA

    Paraformaldehyde

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    Shakhbazau, A., Schenk, G.J., Hay, C. et al. Demyelination induces transport of ribosome-containing vesicles from glia to axons: evidence from animal models and MS patient brains. Mol Biol Rep 43, 495–507 (2016). https://doi.org/10.1007/s11033-016-3990-2

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