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Mechanism of 6‐hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6‐hydroxydopamine‐induced degeneration of dopaminergic neurons
Abstract
Cell death induced by 6‐hydroxydopamine (6‐OHDA) is thought to be caused by reactive oxygen species (ROS) derived from 6‐OHDA autooxidation and by a possible direct effect of 6‐OHDA on the mitochondrial respiratory chain. However, the process has not been totally clarified. In rat primary mesencephalic cultures, we observed a significant increase in dopaminergic (DA) cell loss 24 h after administration of 6‐OHDA (40 μmol/L) and a significant increase in NADPH subunit expression, microglial activation and superoxide anion/superoxide‐derived ROS in DA cells that were decreased by the NADPH inhibitor apocynin. Low doses of 6‐OHDA (10 μmol/L) did not induce a significant loss of DA cells or a significant increase in NADPH subunit expression, microglial activation or superoxide‐derived ROS. However, treatment with the NADPH complex activator angiotensin II caused a significant increase in all the latter. Forty‐eight hours after intrastriatal 6‐OHDA injection in rats, there was still no loss of DA neurons although there was an increase in NADPH subunit expression and NADPH oxidase activity. The results suggest that in addition to the autooxidation‐derived ROS and the inhibition of the mitochondrial respiratory chain, early microglial activation and NADPH oxidase‐derived ROS act synergistically with 6‐OHDA and constitute a relevant and early component of the 6‐OHDA‐induced cell death.
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Cites
Oxidative stress in neurodegeneration: Cause or consequence?
Andersen, J. K. (2004) · Nature Medicine · doi:10.1038/nrn1434 · Cited by 1,869
Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
Block, M. L., & Hong, J.-S. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.004 · Cited by 1,557
Babior, B. M. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2003.12.001 · Cited by 705
Qin, L., Liu, Y., Wang, T., Wei, S.-J., Block, M. L., Wilson, B., Liu, B., & Hong, J.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307657200 · Cited by 574
Tomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203
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Marinova‐Mutafchieva, L., Sadeghian, M., Broom, L., Davis, J. B., Medhurst, A. D., & Dexter, D. T. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06189.x · Cited by 217
Jurado-Coronel, J. C., Cabezas, R., Ávila Rodríguez, M. F., Echeverria, V., García-Segura, L. M., & Barreto, G. E. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.09.002 · Cited by 180
Villar-Cheda, B., Dominguez-Meijide, A., Joglar, B., Rodriguez-Perez, A. I., Guerra, M. J., & Labandeira-Garcia, J. L. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.04.010 · Cited by 104
Self-citationNeuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson disease
Broom, L., Marinova-Mutafchieva, L., Sadeghian, M., Davis, J. B., Medhurst, A. D., & Dexter, D. T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.026 · Cited by 96
Metadata
- Authors
- Rodriguez‐Pallares, J., Parga, J. A., Muñoz, A., Rey, P., Guerra, M. J., & Labandeira‐Garcia, J. L.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-05-22
- Volume
- 103
- Issue
- 1
- Pages
- 145-156
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2071666358
- Cited by
- 231
- References
- 5
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- Rodriguez‐Pallares, J., Parga, J. A., Muñoz, A., Rey, P., Guerra, M. J., & Labandeira‐Garcia, J. L. (2007). Mechanism of 6‐hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6‐hydroxydopamine‐induced degeneration of dopaminergic neurons. Journal of Neurochemistry. https://doi.org/10.1111/j.1471-4159.2007.04699.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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