Effect of in vivo neuronal activity on remyelination
ECTRIMS Online Library. Angulo M. 10/26/17; 202513; 157
Maria Cécilia Angulo
Maria Cécilia Angulo
Contributions
Abstract

Abstract: 157

Type: Oral

Oligodendrocytes precursor cells (OPCs) are a main source of remyelinating oligodendrocytes (OLs) in demyelinating diseases such as Multiple Sclerosis (MS). Although remyelination can occur in MS lesions, it becomes increasingly incomplete and eventually fails with the progression of the disease. Recent reports in different animal models have shown that OLs preferentially myelinate electrically active axons in normal conditions. These findings suggest the interesting possibility that an increased activity of demyelinated axons could modulate oligodendroglia dynamics to increase remyelination. The goal of the present study is to investigate whether an increased axonal activity in vivo modifies the dynamics of OPCs and OLs and promotes remyelination after acute demyelination induced in the adult mouse corpus callosum by focal injection of alpha-lysophosphatidylcholine (LPC). To increase the activity in LPC-demyelinating lesions, we use an optogenetic approach in Thy-1-ChR2-YFP transgenic mice. In these mice, the light-activated protein channelrhodopsin-2 (ChR2) is expressed in cortical layer V pyramidal neurons and thalamic fibers, whose myelinated axons cross the corpus callosum and can be activated by blue light in freely moving mice after LPC-induced demyelination. To determine how neuronal activity in lesions affects OPC and OL dynamics as well as remyelination, we combined optogenetics with immunostainings, extracellular recordings and electron microscopy. We found that in vivo axonal photostimulation promotes remyelination. Our results shed light on the activity-dependent regulation of the remyelination process.
Disclosure: No conflict of interest.
Financial support: Fondation pour la recherche sur la Sclérose en Plaques (ARSEP), Fondation pour la Recherche Médicale (FRM).

Abstract: 157

Type: Oral

Oligodendrocytes precursor cells (OPCs) are a main source of remyelinating oligodendrocytes (OLs) in demyelinating diseases such as Multiple Sclerosis (MS). Although remyelination can occur in MS lesions, it becomes increasingly incomplete and eventually fails with the progression of the disease. Recent reports in different animal models have shown that OLs preferentially myelinate electrically active axons in normal conditions. These findings suggest the interesting possibility that an increased activity of demyelinated axons could modulate oligodendroglia dynamics to increase remyelination. The goal of the present study is to investigate whether an increased axonal activity in vivo modifies the dynamics of OPCs and OLs and promotes remyelination after acute demyelination induced in the adult mouse corpus callosum by focal injection of alpha-lysophosphatidylcholine (LPC). To increase the activity in LPC-demyelinating lesions, we use an optogenetic approach in Thy-1-ChR2-YFP transgenic mice. In these mice, the light-activated protein channelrhodopsin-2 (ChR2) is expressed in cortical layer V pyramidal neurons and thalamic fibers, whose myelinated axons cross the corpus callosum and can be activated by blue light in freely moving mice after LPC-induced demyelination. To determine how neuronal activity in lesions affects OPC and OL dynamics as well as remyelination, we combined optogenetics with immunostainings, extracellular recordings and electron microscopy. We found that in vivo axonal photostimulation promotes remyelination. Our results shed light on the activity-dependent regulation of the remyelination process.
Disclosure: No conflict of interest.
Financial support: Fondation pour la recherche sur la Sclérose en Plaques (ARSEP), Fondation pour la Recherche Médicale (FRM).

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