title: NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation.
abstract: Multipotent cells from the juvenile subventricular zone (SVZ) possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes, or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX) as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.
authors.affiliation: Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU) Leioa, Spain ; Achucarro Basque Center for Neuroscience, Universidad del País Vasco (UPV/EHU) Zamudio, Spain ; Instituto de Salud Carlos III, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas Leioa, Spain.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cavaliere
authors.affiliation: Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU) Leioa, Spain ; Achucarro Basque Center for Neuroscience, Universidad del País Vasco (UPV/EHU) Zamudio, Spain ; Instituto de Salud Carlos III, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas Leioa, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Benito-Muñoz
authors.affiliation: National Centre for Biological Sciences, UAS-GKVK Campus Bangalore, India.
authors.forename: Mitradas
authors.initials: M
authors.lastname: Panicker
authors.affiliation: Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU) Leioa, Spain ; Achucarro Basque Center for Neuroscience, Universidad del País Vasco (UPV/EHU) Zamudio, Spain ; Instituto de Salud Carlos III, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas Leioa, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
keywords: NADPH oxidase; NMDA; PKC; multipotent cell differentiation; reactive oxygen species