Single-Cell Redox Imaging Demonstrates a Distinctive Response of Dopaminergic Neurons to Oxidative Insults
| Autor: | Sara Sepe, Laura M. Montero, Xiaoping Hu, Laurie H. Sanders, J.T. Greenamyre, Roberto Di Maio, Pier G. Mastroberardino, Wiggert A. van Cappellen, Maxx P. Horowitz, Victor Tapias, Chiara Milanese, Edward A. Burton |
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| Přispěvatelé: | Developmental Biology, Molecular Genetics |
| Rok vydání: | 2011 |
| Předmět: |
Physiology
Dopamine Clinical Biochemistry Substantia nigra Oxidative phosphorylation Biology medicine.disease_cause Biochemistry Redox medicine Animals Molecular Biology Cells Cultured Zebrafish General Environmental Science Neurons Brain Mapping Pars compacta Dopaminergic Parkinson Disease Cell Biology Immunohistochemistry Cell biology Rats Substantia Nigra Original Research Communications nervous system Astrocytes General Earth and Planetary Sciences Single-Cell Analysis Reactive Oxygen Species Oxidation-Reduction Oxidative stress Intracellular medicine.drug |
| Zdroj: | Antioxidants & Redox Signaling, 15(4), 855-871. Mary Ann Liebert Inc. |
| ISSN: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2010.3629 |
| Popis: | Aims: The study of the intracellular oxido-reductive (redox) state is of extreme relevance to the dopamine (DA) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production, and they selectively degenerate in Parkinson's disease under oxidative stress conditions. To test the hypothesis that these cells display a unique redox response to mild, physiologically relevant oxidative insults when compared with other neuronal populations, we sought to develop a novel method for quantitatively assessing mild variations in intracellular redox state. Results: We have developed a new imaging strategy to study redox variations in single cells, which is sensitive enough to detect changes within the physiological range. We studied DA neurons' physiological redox response in biological systems of increasing complexity-from primary cultures to zebrafish larvae, to mammalian brains-and identified a redox response that is distinctive for substantia nigra pars compacta DA neurons. We studied simultaneously, and in the same cells, redox state and signaling activation and found that these phenomena are synchronized. Innovation: The redox histochemistry method we have developed allows for sensitive quantification of intracellular redox state in situ. As this method is compatible with traditional immunohistochemical techniques, it can be applied to diverse settings to investigate, in theory, any cell type of interest. Conclusion: Although the technique we have developed is of general interest, these findings provide insights into the biology of DA neurons in health and disease and may have implications for therapeutic intervention. Antioxid. Redox Signal. 15, 855-871. |
| Databáze: | OpenAIRE |
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