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Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults.

Publication ,  Journal Article
Horowitz, MP; Milanese, C; Di Maio, R; Hu, X; Montero, LM; Sanders, LH; Tapias, V; Sepe, S; van Cappellen, WA; Burton, EA; Greenamyre, JT ...
Published in: Antioxid Redox Signal
August 15, 2011

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.

Duke Scholars

Published In

Antioxid Redox Signal

DOI

EISSN

1557-7716

Publication Date

August 15, 2011

Volume

15

Issue

4

Start / End Page

855 / 871

Location

United States

Related Subject Headings

  • Zebrafish
  • Substantia Nigra
  • Single-Cell Analysis
  • Reactive Oxygen Species
  • Rats
  • Parkinson Disease
  • Oxidation-Reduction
  • Neurons
  • Immunohistochemistry
  • Dopamine
 

Citation

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Horowitz, M. P., Milanese, C., Di Maio, R., Hu, X., Montero, L. M., Sanders, L. H., … Mastroberardino, P. G. (2011). Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxid Redox Signal, 15(4), 855–871. https://doi.org/10.1089/ars.2010.3629
Horowitz, Maxx P., Chiara Milanese, Roberto Di Maio, Xiaoping Hu, Laura M. Montero, Laurie H. Sanders, Victor Tapias, et al. “Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults.Antioxid Redox Signal 15, no. 4 (August 15, 2011): 855–71. https://doi.org/10.1089/ars.2010.3629.
Horowitz MP, Milanese C, Di Maio R, Hu X, Montero LM, Sanders LH, et al. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxid Redox Signal. 2011 Aug 15;15(4):855–71.
Horowitz, Maxx P., et al. “Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults.Antioxid Redox Signal, vol. 15, no. 4, Aug. 2011, pp. 855–71. Pubmed, doi:10.1089/ars.2010.3629.
Horowitz MP, Milanese C, Di Maio R, Hu X, Montero LM, Sanders LH, Tapias V, Sepe S, van Cappellen WA, Burton EA, Greenamyre JT, Mastroberardino PG. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxid Redox Signal. 2011 Aug 15;15(4):855–871.
Journal cover image

Published In

Antioxid Redox Signal

DOI

EISSN

1557-7716

Publication Date

August 15, 2011

Volume

15

Issue

4

Start / End Page

855 / 871

Location

United States

Related Subject Headings

  • Zebrafish
  • Substantia Nigra
  • Single-Cell Analysis
  • Reactive Oxygen Species
  • Rats
  • Parkinson Disease
  • Oxidation-Reduction
  • Neurons
  • Immunohistochemistry
  • Dopamine