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Journal of Neuroscience, Vol 15, 3318-3327, Copyright © 1995 by Society for Neuroscience
Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation
IJ Reynolds and TG Hastings
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
Using the fluorescent dye 2',7'-dichlorodihydrofluorescein (DCF-H2) we
investigated the role of glutamate in the production of reactive oxygen
species (ROS) in cultured neurons from fetal rat forebrain. The addition of
an excitotoxic concentration of glutamate (100 microM) produced a
generalized decrease in cellular DCF fluorescence accompanied by local
areas of increased fluorescence around the margins of the cell body that
could be observed within 2-4 min of glutamate exposure. Increases in
fluorescence were dependent on NMDA receptor activation and Ca2+ entry and
were blocked by the mitochondrial proton ionophore carbonyl cyanide
p-trifluoromethoxyphenylhydrazone (FCCP). Additional studies suggested that
the generalized decrease in fluorescence was due to intracellular
acidification. These studies suggest a critical role for mitochondria in
the production of ROS in association with glutamate excitotoxicity, and
additionally demonstrate the feasibility of measuring the production of ROS
at the level of the single cell.
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