Synaptic localization of a functional NADPH oxidase in the mouse hippocampus

Maria V. Tejada-Simon, Faridis Serrano, Laura E. Villasana, Beatriz I. Kanterewicz, Gang Yi Wu, Mark T. Quinn, Eric Klann

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Abstract

Superoxide has been shown to be critical for hippocampal long-term potentiation (LTP) and hippocampus-dependent memory function. A possible source for the generation of superoxide during these processes is NADPH oxidase. The active oxidase consists of two membrane proteins, gp91phox and p22phox, and four cytosolic proteins, p40phox, p47 phox, p67phox, and Rac. Upon stimulation, the cytosolic proteins translocate to the membrane to form a complex with the membrane components, which results in production of superoxide. Here, we determined the presence, localization, and functionality of a NADPH oxidase in mouse hippocampus by examining the NADPH oxidase proteins as well as the production of superoxide. All of the NADPH oxidase proteins were present in hippocampal homogenates and enriched in synaptoneurosome preparations. Immunocytochemical analysis of cultured hippocampal neurons indicated that all NADPH oxidase proteins were localized in neuronal cell bodies as well as dendrites. Furthermore, double labeling analysis using antibodies to p67phox and the presynaptic marker synaptophysin suggest a close association of the NADPH oxidase subunits with synaptic sites. Finally, stimulation of hippocampal slices with phorbol esters triggered translocation of the cytoplasmic NADPH oxidase proteins to the membrane and an increase in superoxide production that was blocked by inhibitors of NADPH oxidase. Taken together, our data suggest that NADPH oxidase is present in mouse hippocampus and might be the source of superoxide production required for LTP and memory function.

Original languageEnglish (US)
Pages (from-to)97-106
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume29
Issue number1
DOIs
StatePublished - May 2005

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ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Tejada-Simon, M. V., Serrano, F., Villasana, L. E., Kanterewicz, B. I., Wu, G. Y., Quinn, M. T., & Klann, E. (2005). Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Molecular and Cellular Neuroscience, 29(1), 97-106. https://doi.org/10.1016/j.mcn.2005.01.007