ECTRIMS eLearning

Identification of oligodendroglial secreted factors inducing nodal protein clustering in the central nervous system
Author(s): ,
A.-L. Dubessy
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière; GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris
,
E. Mazuir
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière
,
L. Richevaux
Affiliations:
Centre de Neurophysique, Physiologie, Pathologies, CNRS UMR 8119 Université Paris Descartes, Paris, France
,
Q. Rappeneau
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière
,
S. Ou
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière; GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris
,
A. Desmazières
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière; GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris
,
B. Zalc
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière
,
D. Fricker
Affiliations:
Centre de Neurophysique, Physiologie, Pathologies, CNRS UMR 8119 Université Paris Descartes, Paris, France
,
B. Ranscht
Affiliations:
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States
,
C. Lubetzki
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière; GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris
N. Sol-Foulon
Affiliations:
ICM, F-75013, Sorbonne Université, Inserm, CNRS, UMR7225, Institut du Cerveau et de la Moelle Épinière
ECTRIMS Learn. Mazuir E. 10/10/18; 228297; P453
Elisa Mazuir
Elisa Mazuir
Contributions
Abstract

Abstract: P453

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurobiology

The fast and reliable propagation of action potentials along myelinated fibers relies on the clustering of voltage-gated sodium channels (Nav) at the nodes of Ranvier. Our recent study uncovered the influence of oligodendroglial secreted factors for nodal protein clustering before myelination (i.e. prenodes) on hippocampal interneurons and extended to electrophysiological characterization and in vivo relevance (Freeman et al., 2015). We further characterized the oligodendrocyte-conditioned medium (OCM) activity and found that addition of a combination of recombinant cell adhesion molecule and extracellular matrix proteins on purified neuron culture is sufficient to induce Nav clustering in the absence of oligodendrocytes. Furthermore, inhibition of the protein activity in the OCM, using an immunodepletion approach and knock out models, reduces its clustering activity. Altogether this suggests that early events of nodal protein clustering result in a complex interplay of cell adhesion molecules and extracellular matrix proteins. Moreover, to further characterize the intrinsic neuronal properties within the cells that develops nodes prior to myelination, we analyzed their electrophysiological properties. We also use a gene expression analysis approach to compare gene expression in hippocampal neurons with and without prenodes. This could allow for identification of specific roles for oligodendrocytes or their precursors in the developing nervous system and interactions that mediate myelination of interneurons.
Disclosure: Anne-Laure Dubessy : nothing to disclose
Elisa Mazuir : nothing to disclose
Louis Richevaux : nothing to disclose
Quentin Rappeneau : nothing to disclose
Sokounthie Ou : nothing to disclose
Anne Desmazières : nothing to disclose
Bernard Zalc : nothing to disclose
Desdemona Fricker : nothing to disclose
Barbara Ranscht : nothing to disclose
Catherine Lubetzki : nothing to disclose
Nathalie Sol-Foulon : nothing to disclose

Abstract: P453

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurobiology

The fast and reliable propagation of action potentials along myelinated fibers relies on the clustering of voltage-gated sodium channels (Nav) at the nodes of Ranvier. Our recent study uncovered the influence of oligodendroglial secreted factors for nodal protein clustering before myelination (i.e. prenodes) on hippocampal interneurons and extended to electrophysiological characterization and in vivo relevance (Freeman et al., 2015). We further characterized the oligodendrocyte-conditioned medium (OCM) activity and found that addition of a combination of recombinant cell adhesion molecule and extracellular matrix proteins on purified neuron culture is sufficient to induce Nav clustering in the absence of oligodendrocytes. Furthermore, inhibition of the protein activity in the OCM, using an immunodepletion approach and knock out models, reduces its clustering activity. Altogether this suggests that early events of nodal protein clustering result in a complex interplay of cell adhesion molecules and extracellular matrix proteins. Moreover, to further characterize the intrinsic neuronal properties within the cells that develops nodes prior to myelination, we analyzed their electrophysiological properties. We also use a gene expression analysis approach to compare gene expression in hippocampal neurons with and without prenodes. This could allow for identification of specific roles for oligodendrocytes or their precursors in the developing nervous system and interactions that mediate myelination of interneurons.
Disclosure: Anne-Laure Dubessy : nothing to disclose
Elisa Mazuir : nothing to disclose
Louis Richevaux : nothing to disclose
Quentin Rappeneau : nothing to disclose
Sokounthie Ou : nothing to disclose
Anne Desmazières : nothing to disclose
Bernard Zalc : nothing to disclose
Desdemona Fricker : nothing to disclose
Barbara Ranscht : nothing to disclose
Catherine Lubetzki : nothing to disclose
Nathalie Sol-Foulon : nothing to disclose

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