Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate
Open accessAbstract
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.
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NMDAR activation promotes the differentiation of cultured oligodendrocytes via NOX-mediated reactive oxygen species.
“Interestingly, NMDAR activation promotes the differentiation of cultured oligodendrocytes via NOX-mediated ROS (Cavaliere et al., 2012).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Cavaliere et al., 2012
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CNS stem cells express a new class of intermediate filament protein
Lendahl, U., Zimmerman, L. B., & McKay, R. D. G. (1990) · Cell · doi:10.1016/0092-8674(90)90662-x · Cited by 3,164 · see citing works
Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity
Nishiyama, A., Komitova, M., Suzuki, R., & Zhu, X. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2495 · Cited by 865 · see citing works
Le Belle, J. E., Orozco, N. M., Paucar, A. A., Saxe, J. P., Mottahedeh, J., Pyle, A. D., Wu, H., & Kornblum, H. I. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.11.028 · Cited by 789 · see citing works
NMDA receptors are expressed in oligodendrocytes and activated in ischaemia
Káradóttir, R. T., Cavelier, P., Bergersen, L. H., & Attwell, D. (2005) · Nature · doi:10.1038/nature04302 · Cited by 773 · see citing works
Mechanisms of Neuronal Dysfunction and Degeneration in Multiple Sclerosis
Dutta, R., & Trapp, B. (2010) · Progress in neurobiology · doi:10.1016/j.pneurobio.2010.09.005 · Cited by 453 · see citing works
Pigment epithelium–derived factor is a niche signal for neural stem cell renewal
Ramírez‐Castillejo, C., Sánchez‐Sánchez, F., Andreu-Agulló, C., Ferrón, S. R., Aroca‐Aguilar, J., Sánchez‐Gómez, P., Mira, H., Escribano, J., & Fariñas, I. (2006) · Nature Neuroscience · doi:10.1038/nn1657 · Cited by 446 · see citing works
Sucher, N. J., Akbarian, S., Chi, C.-L., Leclerc, C., Awobuluyi, M., Deitcher, D. L., Wu, M., Yuan, J., Jones, E. G., & Lipton, S. A. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-10-06509.1995 · Cited by 420 · see citing works
PEDF: a multifaceted neurotrophic factor
Tombran‐Tink, J., & Barnstable, C. J. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1176 · Cited by 369 · see citing works
Mechanism of differential control of NMDA receptor activity by NR2 subunits
Gielen, M. C., Retchless, B. S., Mony, L., Johnson, J. W., & Paoletti, P. (2009) · Nature · doi:10.1038/nature07993 · Cited by 325 · see citing works
Watkins, T. A., Emery, B., Mulinyawe, S. B., & Barres, B. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.011 · Cited by 317 · see citing works
Yoshihara, Y., Kawasaki, M., Tamada, A., Fujita, H., Hayashi, H., Kagamiyama, H., & Mori, K. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05830.1997 · Cited by 299 · see citing works
Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors
Pérez‐Otaño, I., Schulteis, C. T., Contractor, A., Lipton, S. A., Trimmer, J. S., Sucher, N. J., & Heinemann, S. F. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-04-01228.2001 · Cited by 287 · see citing works
Regional modulation of neurofilament organization by myelination in normal axons
Hsieh, S., Kidd, G. J., Crawford, T., Xu, Z., Lin, W., Trapp, B., Cleveland, D. W., & Griffin, J. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-11-06392.1994 · Cited by 238 · see citing works
Polydendrocytes: NG2 Cells with Many Roles in Development and Repair of the CNS
Nishiyama, A. (2007) · The Neuroscientist · doi:10.1177/1073858406295586 · Cited by 179 · see citing works
Lee, J., Gravel, M., Zhang, R., Thibault, P., & Braun, P. E. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200411047 · Cited by 175 · see citing works
Rules of engagement for NMDA receptor subunits
Ulbrich, M. H., & Isacoff, E. Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802075105 · Cited by 174 · see citing works
Cheung, N. S., Pascoe, C. J., Giardina, S. F., John, C. A., & Beart, P. M. (1998) · Neuropharmacology · doi:10.1016/s0028-3908(98)00123-3 · Cited by 173 · see citing works
Brazel, C. Y., Nuñez, J. L., Yang, Z., & Levison, S. W. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.10.038 · Cited by 156 · see citing works
Increased expression and function of glutamate transporters in multiple sclerosis
Vallejo‐Illarramendi, A., Domercq, M., Pérez‐Cerdá, F., Ravid, R., & Matute, C. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.06.017 · Cited by 146 · see citing works
Self-citationAxons and astrocytes release ATP and glutamate to evoke calcium signals in NG2‐glia
Hamilton, N. B., Vayro, S., Wigley, R., & Butt, A. M. (2009) · Glia · doi:10.1002/glia.20902 · Cited by 144 · see citing works
NADPH oxidase is required for NMDA receptor‐dependent activation of ERK in hippocampal area CA1
Kishida, K. T., Pao, M., Holland, S. M., & Klann, E. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03189.x · Cited by 135 · see citing works
Characterization of a Soluble Ligand Binding Domain of the NMDA Receptor Regulatory Subunit NR3A
Yao, Y., & Mayer, M. L. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0560-06.2006 · Cited by 120 · see citing works
Activation of Kainate Receptors Sensitizes Oligodendrocytes to Complement Attack
Alberdi, E. M., Sánchez‐Gómez, M. V., Torre, I., Domercq, M., Pérez‐Samartín, A., Pérez‐Cerdá, F., & Matute, C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3780-05.2006 · Cited by 93 · see citing works
Self-citationChemically Diverse Toxicants Converge on Fyn and c-Cbl to Disrupt Precursor Cell Function
Li, Z., Dong, T., Pröschel, C., & Noble, M. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050035 · Cited by 90 · see citing works
Oligodendrocyte NMDA receptors: a novel therapeutic target
Matute, C. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.05.004 · Cited by 81 · see citing works
Self-citationConsiderations in the treatment of relapsing-remitting multiple sclerosis
Calabresi, P. A. (2002) · Neurology · doi:10.1212/wnl.58.8_suppl_4.s10 · Cited by 57 · see citing works
Larm, J. A., Cheung, N. S., & Beart, P. M. (1996) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00633-4 · Cited by 36 · see citing works
Palliative care for multiple sclerosis: a counter-intuitive approach?
Voltz, R. (2010) · Multiple Sclerosis Journal · doi:10.1177/1352458510367466 · Cited by 25 · see citing works
Namba, T., Yabe, T., Gonda, Y., Ichikawa, N., Sanagi, T., Arikawa‐Hirasawa, E., Mochizuki, H., Kohsaka, S., & Uchino, S. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.033 · Cited by 23 · see citing works
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Steullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., & Do, K. Q. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.021 · Cited by 262 · see citing works
Monin, A., Baumann, P. S., Griffa, A., Xin, L., Mekle, R., Fournier, M., Butticaz, C., Klaey, M., Cabungcal, J. H., Steullet, P., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.88 · Cited by 113 · see citing works
- Authors
- Cavaliere, F., Urra, O., Alberdi, E., & Matute, C.
- Affiliations
- University of the Basque Country (ES)
- Corresponding author
- Matute, C
- Venue
- Cell Death & Disease
- Published
- 2012-02-02
- Volume
- 3
- Issue
- 2
- Pages
- e268-e268
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3288341
- OpenAlex
- W2071496882
- Cited by
- 69
- References
- 29
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 12 · 2012: 4
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Communities in ADDI (University of the Basque Country) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- Hispana (submittedVersion, cc-by-nc-nd)
- Funders
- Eusko Jaurlaritza
- Ministerio de Ciencia e Innovación (SAF2010-21547)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- oligodendrocyte differentiation, glutamate, NMDA receptor, NMDAR1, NMDAR2B, reactive oxygen species, NADPH oxidase, apocynin, intracellular calcium, myelination, oligodendrocyte maturation
- MeSH terms
- Acetophenones, Animals, Animals, Newborn, Calcium, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Myelin Sheath, Neurons, Oligodendroglia, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Reactive Oxygen Species, Glutamic Acid, Coculture Techniques, NADPH Oxidases, Protein Isoforms, Multipotent Stem Cells, Rats, Adult Stem Cells
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