期刊
BRAIN RESEARCH
卷 1476, 期 -, 页码 164-171出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2012.07.059
关键词
Ketamine; Extracellular signal-regulated kinase; Protein kinase C gamma; Neurodegeneration; Hippocampus
资金
- Libang Scientific Research Funds of Chinese Medical Association Anesthesiology Society [CSA2010LB017]
- Key Medicine Scientific Developing Program of Hebei Province [20110338]
Ketamine, an N-methyl-o-aspartate (NMDA) receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggest that ketamine enhances neuronal apoptosis in developing rodents and nonhuman primates. The main goal of this study is to determine whether ketamine. causes hippocampal neurodegeneration and behavioral deficits in adulthood, and if so, whether the effects of ketamine are associated with protein kinase C-gamma (PKC gamma), extracellular signal regulated kinase (ERK)1/2 and Bcl-2 expression. Starting from postnatal day 7, Sprague-Dawley rat pups randomly received daily ketamine treatment (25, 50 and 75 mg/kg, ip) for three consecutive days. Twenty-four hours after the last treatment with ketamine, the rats were decapitated, and the hippocampi were isolated for detection of neuronal apoptosis by TUNEL. The protein expression levels of PKC gamma, ERK1/2 and Bcl-2 in the hippocampi were measured by western blot analysis. At 2 months of age, learning and memory abilities were tested by the Morris water maze. Ketamine increased the number of apoptotic cells in the CA1 region and dentate gyrus at a dose of 75 mg/kg but not at lower doses of 25 and 50 mg/kg. The dose of 75 mg/kg of ketamine suppressed p-PKC, p-ERK1/2 and Bcl-2 expression but not t-PKC or t-ERK expression. Ketamine administered to the developing brains of P7 rats at a dose of 75 mg/kg caused learning and memory impairments in adulthood. Therefore, these data demonstrate that ketamine at a dose of 75 mg/kg in the developing brain results in hippocampal neurodegeneration and persistent learning and memory impairment, which is associated with the PKC gamma-ERK signaling pathway. This article is part of a Special Issue entitled: Brain Integration. (C) 2012 Elsevier B.V. All rights reserved.
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