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Neuron. 2014 Dec 17;84(6):1183-90. doi: 10.1016/j.neuron.2014.11.006. Epub 2014 Nov 26.

Pervasive axonal transport deficits in multiple sclerosis models.

Author information

1
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Marchioninistraße 17, 81377 Munich, Germany; Institute of Neuronal Cell Biology, Technische Universität München, Biedersteiner Straße 29, 80802 Munich, Germany.
2
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Marchioninistraße 17, 81377 Munich, Germany.
3
Department of Pathology and Immunology, University of Geneva, Rue Michel Servet 1, 1211 Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland; Department of Neuropathology, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany.
4
Institute of Neuronal Cell Biology, Technische Universität München, Biedersteiner Straße 29, 80802 Munich, Germany.
5
Transgenic Core Facility, Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
6
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Marchioninistraße 17, 81377 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 Munich, Germany.
7
Department of Physiology, Indiana University School of Medicine-Muncie, Cooper Science Building, CL 215, Muncie, IN 47306, USA.
8
Institute of Neuronal Cell Biology, Technische Universität München, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Straße 17, 81377 Munich, Germany; Center of Integrated Protein Science (CIPSM), Butenandtstraße 5-13, 81377 Munich, Germany. Electronic address: thomas.misgeld@lrz.tu-muenchen.de.
9
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Marchioninistraße 17, 81377 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 Munich, Germany. Electronic address: martin.kerschensteiner@med.uni-muenchen.de.

Abstract

Impaired axonal transport can contribute to axon degeneration and has been described in many neurodegenerative diseases. Multiple sclerosis (MS) is a common neuroinflammatory disease, which is characterized by progressive axon degeneration-whether, when, and how axonal transport is affected in this condition is unknown. Here we used in vivo two-photon imaging to directly assay transport of organelles and the stability of microtubule tracks in individual spinal axons in mouse models of MS. We found widespread transport deficits, which preceded structural alterations of axons, cargos, or microtubules and could be reversed by acute anti-inflammatory interventions or redox scavenging. Our study shows that acute neuroinflammation induces a pervasive state of reversible axonal dysfunction, which coincides with acute disease symptoms. Moreover, perpetuated transport dysfunction, as we found in a model of progressive MS, led to reduced distal organelle supply and could thus contribute to axonal dystrophy in advanced stages of the disease.

PMID:
25433639
DOI:
10.1016/j.neuron.2014.11.006
[Indexed for MEDLINE]
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