Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease.
Mol Cell Biol
; 26(15): 5908-20, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16847341
ABSTRACT
Reactive oxygen species (ROS) are required in a number of critical cellular signaling events, including those underlying hippocampal synaptic plasticity and hippocampus-dependent memory; however, the source of ROS is unknown. We previously have shown that NADPH oxidase is required for N-methyl-D-aspartate (NMDA) receptor-dependent signal transduction in the hippocampus, suggesting that NADPH oxidase may be required for NMDA receptor-dependent long-term potentiation (LTP) and hippocampus-dependent memory. Herein we present the first evidence that NADPH oxidase is involved in hippocampal synaptic plasticity and memory. We have found that pharmacological inhibitors of NADPH oxidase block LTP. Moreover, mice that lack the NADPH oxidase proteins gp91(phox) and p47(phox), both of which are mouse models of human chronic granulomatous disease (CGD), also lack LTP. We also found that the gp91(phox) and p47(phox) mutant mice have mild impairments in hippocampus-dependent memory. The gp91(phox) mutant mice exhibited a spatial memory deficit in the Morris water maze, and the p47(phox) mutant mice exhibited impaired context-dependent fear memory. Taken together, our results are consistent with NADPH oxidase being required for hippocampal synaptic plasticity and memory and are consistent with reports of cognitive dysfunction in patients with CGD.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Potenciação de Longa Duração
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Doença Granulomatosa Crônica
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Memória
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Plasticidade Neuronal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos