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JCI Insight. 2019 Mar 21;5. pii: 123434. doi: 10.1172/jci.insight.123434.

Neuronal activity in vivo enhances functional myelin repair.

Author information

1
INSERM U1128, Paris, France.
2
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
3
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
4
Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, Paris, France.
5
Institut du Cerveau et de la Moelle épinière, Sorbonne Université, INSERM U1127, CNRS UMR 7225, Paris, France.
6
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.

Abstract

In demyelinating diseases such as Multiple Sclerosis (MS), demyelination of neuronal fibers impairs impulse conduction and causes axon degeneration. While neuronal activity stimulates oligodendrocyte production and myelination in normal conditions, it remains unclear whether the activity of demyelinated axons restores their loss-of-function in a harmful environment. To investigate this question, we established a model to induce a moderate optogenetic stimulation of demyelinated axons in the corpus callosum at the level of the motor cortex in which cortical circuit activation and locomotor effects were reduced in adult freely moving mice. We demonstrate that a moderate activation of demyelinated axons enhances the differentiation of oligodendrocyte precursor cells onto mature oligodendrocytes, but only under a repeated stimulation paradigm. This activity-dependent increase in the oligodendrocyte pool promotes an extensive remyelination and functional restoration of conduction, as revealed by ultrastructural analyses and compound action potential recordings. Our findings reveal the need of preserving an appropriate neuronal activity in the damaged tissue to promote oligodendrocyte differentiation and remyelination, likely by enhancing axon-oligodendroglia interactions. Our results provide new perspectives for translational research using neuromodulation in demyelinating diseases.

KEYWORDS:

Demyelinating disorders; Neuroscience

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