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

Deletion of the life span determinant p66Shc prevents age-dependent increases in emotionality and pain sensitivity in mice
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DOI:
10.1016/j.exger.2006.05.018
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发表时间:
2007-01-01
影响因子:
3.9
通讯作者:
Cirulli, Francesca
Cirulli, Francesca
中科院分区:
医学2区
文献类型:
--
作者:
Berry, Alessandra;Capone, Francesca;Cirulli, Francesca

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氧化应激与衰老过程有关。先前的研究已经确定,具有p66(She)基因靶向突变的小鼠表现出减少的氧化应激和延长的寿命。这项研究是携带p66(She)缺失的小鼠的第一个行为特征。对129 sv/Ev品系的4个月、11个月和24个月大的纯合敲除和野生型小鼠进行了一系列行为测试。在旷场试验中测试运动和探索活动,在高架十字迷宫中评估情绪反应,而通过热板试验(50 ℃)评估伤害感受。此外,在社会互动测试中评估了社会行为。我们的研究结果表明,野生型小鼠的疼痛敏感性和情绪行为随着年龄的增长而增加。p66基因的缺失导致疼痛阈值的增加和情绪性的降低,与野生型受试者的差异随着年龄的增长而变得更加明显。因此,在整个生命周期中减少氧化应激能够防止衰老的一些行为影响,特别是在对疼痛或情绪刺激的反应中。这些数据进行了讨论,最近的观点,表明新的和复杂的氧化应激和情绪压力之间的相互作用。(c)2006年爱思唯尔公司All rights reserved.
Oxidative stress has been implicated in the aging process. Previous studies have determined that mice with a targeted mutation of the p66(She) gene show reduced oxidative stress and extended life span. This study is the first behavioral characterization of mice carrying a deletion of p66(She). 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. (c) 2006 Elsevier Inc. All rights reserved.