Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate.
We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination.
Department of Neurosciences and CIBERNED, University of Basque Country-UPV/EHU, E-48940 Leioa, Spain.
F
F
Cavaliere
O
O
Urra
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E
Alberdi
C
C
Matute
D000098:Acetophenones / Q000494:pharmacology; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000494:pharmacology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D000098:Acetophenones; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C056165:acetovanillone; D019255:NADPH Oxidases; D002118:Calcium