Alteration of Synaptic Connectivity of Oligodendrocyte Precursor Cells Following Demyelination

Frontiers in Cellular Neuroscience

Aurélia eSahel¹  Christophe eKerninon¹  Brahim eNait-Oumesmar¹  Fernando C. Ortiz⁵  Paloma P. Maldonado⁵  María Cecilia eAngulo⁵ 

[1] CNRS UMR 7225;INSERM U1128;Inserm U 1127, Institut du Cerveau et de la Moelle Epinière;Université Paris 6, Sorbonne Paris Cité, UMR-S1127,;Université Paris Descartes, Sorbonne Paris Cité;

关键词: Multiple Sclerosis;    oligodendrocyte;    demyelination;    oligodendrocyte precursor cells;    NG2 cells;    Neuron-OPC synapses;   

DOI  :  10.3389/fncel.2015.00077

来源: DOAJ

【 摘 要 】

Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating oligodendrocytes in demyelinating diseases such as multiple sclerosis (MS). While OPCs are innervated by unmyelinated axons in the normal brain, the fate of such synaptic contacts after demyelination is still unclear. By combining electrophysiology and immunostainings in different transgenic mice expressing fluorescent reporters, we studied the synaptic innervation of OPCs in the model of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic innervation of reactivated OPCs in the lesion was revealed by the presence of AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D confocal reconstructions and synaptic junctions observed by electron microscopy. Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the existence of glutamatergic axon-OPC contacts in post-mortem MS lesions. Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a drastic decrease in spontaneous synaptic activity of OPCs early after demyelination that was not caused by an impaired conduction of compound action potentials. A reduction in synaptic connectivity was confirmed by the lack of VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation phase in lesions, the proportion of innervated OPCs rapidly recovers, although the frequency of spontaneous synaptic currents did not reach control levels. In conclusion, our results demonstrate that newly-generated OPCs do not receive synaptic inputs during their active proliferation after demyelination, but gain synapses during the remyelination process. Hence, glutamatergic synaptic inputs may contribute to inhibit OPC proliferation and might have a physiopathological relevance in demyelinating disorders.

【 授权许可】

Unknown