Method for identifying neuronal cells suffering zinc toxicity by use of a novel fluorescent sensor

Christopher J. Frederickson, Shawn C. Burdette, Cathy J. Frederickson, Stefano L. Sensi, John H. Weiss, Hong Z. Yin, Rengarajan V. Balaji, Ai Q. Truong-Tran, Eric Bedell, Donald Prough, Stephen J. Lippard

Research output: Contribution to journalArticle

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Abstract

During excitotoxic brain damage, injured neurons accumulate an anomalous, pathological burden of weakly bound, rapidly exchangeable Zn2+ that diffusely fills the soma, nucleus and proximal dendrites. Mounting evidence indicates that this Zn2+ is a major contributing factor in the subsequent demise of the damaged neurons. Thus, identifying, imaging, and characterizing zinc-filled cells have become essential steps in understanding excitotoxicity. Here we demonstrate that a new fluorescent stain for zinc can rather selectively and quite vividly label zinc-filled neurons in frozen histologic sections. The method is more sensitive and selective than the existing stain TSQ, and simpler than the Timm-Danscher silver staining techniques. A previously unobserved population of apparently injured cells in the dentate gyrus has been discovered with the new reagent. Whereas cells viewed in situ in normal, healthy tissue virtually never display any perikaryal staining by histochemical methods for zinc [Histochemistry, 71 (1981) 1; Int. Rev. Neurobiol. 31 (1989) 145], injured cells stain intensely for zinc in culture [J. Neurosci. 17 (1997) 9554], acute slice preparations [J. Histochem. Cytochem. 47 (1999) 969; J. Neurosci. 22 (2002) 1273] and in tissue harvested in vivo [Science 272 (1996) 1013; Annu. Rev. Neurosci. 21 (1998) 347]. Thus, the presence of rapidly-exchangeable, "stainable" perikaryal zinc may be taken as an indicator of cell injury [J. Nutr. 130 (2000) 1471S; Biometals 14 (2001) 353].

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalJournal of Neuroscience Methods
Volume139
Issue number1
DOIs
StatePublished - Oct 15 2004

Fingerprint

Zinc
Coloring Agents
Neurons
Silver Staining
Dentate Gyrus
Trace Elements
Frozen Sections
Carisoprodol
Dendrites
Staining and Labeling
Wounds and Injuries
Brain
Population

Keywords

  • Brain injury
  • Damaged neurons
  • Dentate gyrus
  • Excitotoxicity
  • New cells
  • Subgranular strata
  • Zinc-specific sensor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Frederickson, C. J., Burdette, S. C., Frederickson, C. J., Sensi, S. L., Weiss, J. H., Yin, H. Z., ... Lippard, S. J. (2004). Method for identifying neuronal cells suffering zinc toxicity by use of a novel fluorescent sensor. Journal of Neuroscience Methods, 139(1), 79-89. https://doi.org/10.1016/j.jneumeth.2004.04.033

Method for identifying neuronal cells suffering zinc toxicity by use of a novel fluorescent sensor. / Frederickson, Christopher J.; Burdette, Shawn C.; Frederickson, Cathy J.; Sensi, Stefano L.; Weiss, John H.; Yin, Hong Z.; Balaji, Rengarajan V.; Truong-Tran, Ai Q.; Bedell, Eric; Prough, Donald; Lippard, Stephen J.

In: Journal of Neuroscience Methods, Vol. 139, No. 1, 15.10.2004, p. 79-89.

Research output: Contribution to journalArticle

Frederickson, CJ, Burdette, SC, Frederickson, CJ, Sensi, SL, Weiss, JH, Yin, HZ, Balaji, RV, Truong-Tran, AQ, Bedell, E, Prough, D & Lippard, SJ 2004, 'Method for identifying neuronal cells suffering zinc toxicity by use of a novel fluorescent sensor', Journal of Neuroscience Methods, vol. 139, no. 1, pp. 79-89. https://doi.org/10.1016/j.jneumeth.2004.04.033
Frederickson, Christopher J. ; Burdette, Shawn C. ; Frederickson, Cathy J. ; Sensi, Stefano L. ; Weiss, John H. ; Yin, Hong Z. ; Balaji, Rengarajan V. ; Truong-Tran, Ai Q. ; Bedell, Eric ; Prough, Donald ; Lippard, Stephen J. / Method for identifying neuronal cells suffering zinc toxicity by use of a novel fluorescent sensor. In: Journal of Neuroscience Methods. 2004 ; Vol. 139, No. 1. pp. 79-89.
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AU - Yin, Hong Z.

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N2 - During excitotoxic brain damage, injured neurons accumulate an anomalous, pathological burden of weakly bound, rapidly exchangeable Zn2+ that diffusely fills the soma, nucleus and proximal dendrites. Mounting evidence indicates that this Zn2+ is a major contributing factor in the subsequent demise of the damaged neurons. Thus, identifying, imaging, and characterizing zinc-filled cells have become essential steps in understanding excitotoxicity. Here we demonstrate that a new fluorescent stain for zinc can rather selectively and quite vividly label zinc-filled neurons in frozen histologic sections. The method is more sensitive and selective than the existing stain TSQ, and simpler than the Timm-Danscher silver staining techniques. A previously unobserved population of apparently injured cells in the dentate gyrus has been discovered with the new reagent. Whereas cells viewed in situ in normal, healthy tissue virtually never display any perikaryal staining by histochemical methods for zinc [Histochemistry, 71 (1981) 1; Int. Rev. Neurobiol. 31 (1989) 145], injured cells stain intensely for zinc in culture [J. Neurosci. 17 (1997) 9554], acute slice preparations [J. Histochem. Cytochem. 47 (1999) 969; J. Neurosci. 22 (2002) 1273] and in tissue harvested in vivo [Science 272 (1996) 1013; Annu. Rev. Neurosci. 21 (1998) 347]. Thus, the presence of rapidly-exchangeable, "stainable" perikaryal zinc may be taken as an indicator of cell injury [J. Nutr. 130 (2000) 1471S; Biometals 14 (2001) 353].

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