NADPH oxidase is required for NMDA receptor‐dependent activation of ERK in hippocampal area CA1

• Published in: Journal of neurochemistry 2005-07, Vol.94 (2), p.299-306
• Main Authors: Kishida, Kenneth T., Pao, Maryland, Holland, Steven M., Klann, Eric
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Acetylcysteine - analogs & derivatives; Acetylcysteine - pharmacology; Acids; Animals; Azoles - pharmacology; Biological and medical sciences; Blotting, Western - methods; Brain; Catalase - pharmacology; Catecholamines - pharmacology; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine Agonists; Drug Interactions; Enzyme Activation - drug effects; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Enzymes; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Excitatory Postsynaptic Potentials - radiation effects; Extracellular Signal-Regulated MAP Kinases - classification; Extracellular Signal-Regulated MAP Kinases - metabolism; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampus - cytology; Hippocampus - enzymology; Imidazolines - pharmacology; In Vitro Techniques; learning and memory; long‐term potentiation; Lysine - analogs & derivatives; Lysine - pharmacology; Metalloporphyrins - pharmacology; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); N-Methylaspartate - pharmacology; NADPH Oxidases - metabolism; Neurology; Neurons - drug effects; Neurons - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Organoselenium Compounds - pharmacology; oxygen species; Patch-Clamp Techniques - methods; Phosphorylation - drug effects; reactive; Reactive Oxygen Species - metabolism; Receptors, N-Methyl-D-Aspartate - physiology; superoxide; Superoxide Dismutase - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03189.x

Previous studies have shown that N‐methyl‐d‐aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal‐regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor‐dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor‐dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N‐acetyl‐l‐cysteine (L‐NAC), the superoxide‐scavenging enzyme superoxide dismutase (SOD), the membrane‐permeable SOD mimetic Mn(III) tetrakis (4‐benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide‐scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor‐dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor‐dependent activation of ERK in hippocampal area CA1.