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Deletion of the life span determinant p66Shc prevents age-dependent increases in emotionality and pain sensitivity in mice.

作者信息

Berry Alessandra, Capone Francesca, Giorgio Marco, Pelicci Pier Giuseppe, de Kloet E R, Alleva Enrico, Minghetti Luisa, Cirulli Francesca

机构信息

Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, I-00161 Rome, Italy.

出版信息

Exp Gerontol. 2007 Jan-Feb;42(1-2):37-45. doi: 10.1016/j.exger.2006.05.018. Epub 2006 Jun 30.

DOI:10.1016/j.exger.2006.05.018
PMID:16809014
Abstract

Oxidative stress has been implicated in the aging process. Previous studies have determined that mice with a targeted mutation of the p66(Shc) gene show reduced oxidative stress and extended life span. This study is the first behavioral characterization of mice carrying a deletion of p66(Shc). Four-, 11- and 24-months-old homozygous knockout and wild-type mice of the 129Sv/Ev strain underwent a battery of behavioral tests. Locomotion and exploratory activity were tested in the open-field test, emotional reactivity was assessed in the elevated plus-maze, while nociception was evaluated by means of the hot-plate test (50 degrees C). In addition, social behavior was assessed in a social interaction test. Our results indicate that pain sensitivity and emotional behavior in wild-type mice increase with age. Deletion of the p66 gene results in an increase in pain threshold and reduced emotionality, differences with wild-type subjects becoming more pronounced with age. Thus reduced oxidative stress throughout the life span is able to prevent some behavioral effects of aging, particularly in response to painful or emotionally arousing stimuli. These data are discussed in relation to recent views, indicating new and complex interactions between oxidative stress and emotional stress.

摘要

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Deletion of the life span determinant p66Shc prevents age-dependent increases in emotionality and pain sensitivity in mice.
Exp Gerontol. 2007 Jan-Feb;42(1-2):37-45. doi: 10.1016/j.exger.2006.05.018. Epub 2006 Jun 30.
2
Deletion of the lifespan determinant p66(Shc) improves performance in a spatial memory task, decreases levels of oxidative stress markers in the hippocampus and increases levels of the neurotrophin BDNF in adult mice.寿命决定因子p66(Shc)的缺失改善了成年小鼠在空间记忆任务中的表现,降低了海马体中氧化应激标志物的水平,并提高了神经营养因子BDNF的水平。
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Deletion of p66shc gene protects against age-related endothelial dysfunction.p66shc基因的缺失可预防与年龄相关的内皮功能障碍。
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Sustained hippocampal neurogenesis in females is amplified in P66(Shc-/-) mice: An animal model of healthy aging.P66(Shc-/-) 小鼠中持续的海马神经发生增强:一种健康衰老的动物模型。
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Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet.p66Shc长寿基因的缺失可降低高脂饮食喂养小鼠的全身和组织氧化应激、血管细胞凋亡及早期动脉粥样硬化的发生。
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Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress.p66(Shc)衔接蛋白的基因缺失可预防高血糖诱导的内皮功能障碍和氧化应激。
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5217-22. doi: 10.1073/pnas.0609656104. Epub 2007 Mar 14.
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Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein.衰老与心血管疾病的最终共同分子途径:p66Shc蛋白的作用
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The mammalian longevity-associated gene product p66shc regulates mitochondrial metabolism.哺乳动物长寿相关基因产物p66shc调节线粒体代谢。
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Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress.糖尿病诱导人外周血单个核细胞中p66shc基因表达:与氧化应激的关系。
J Clin Endocrinol Metab. 2005 Feb;90(2):1130-6. doi: 10.1210/jc.2004-1283. Epub 2004 Nov 23.
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The p66shc adaptor protein controls oxidative stress response and life span in mammals.p66shc衔接蛋白控制哺乳动物的氧化应激反应和寿命。
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