Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits.

Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits.
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DOI:
10.1016/j.brainres.2020.146697
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发表时间:
2020-05-01
期刊:
影响因子:
2.9
通讯作者:
Skelton MR
Skelton MR
中科院分区:
医学3区
文献类型:
--
作者:
Miles KN;Skelton MR

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生酮饮食(KD)是一种针对特定类型癫痫的非药物治疗方法。此外,它已被证明对减轻其他神经系统疾病有效。KD在减少体重方面也很有效,导致普通人群减肥使用的增加。随着KD在临床和一般应用的普及,开发适当的小鼠模型以更好地了解KD在正常和病变状态下的作用是很重要的。很多时候,用KD治疗的疾病的最佳结果是在生命早期开始治疗。很少有研究评估在生命早期开始KD的认知效果。为了更好地理解这些影响,雄性C57BL6/J小鼠从出生后(P) 21天(~P90)开始被置于KD中。与喂食对照饮食(CD)的小鼠相比,喂食kd的小鼠血酮水平升高,血糖降低,体重增加减少。喂食kd的小鼠体重减轻并没有伴随着体脂百分比的变化,这表明瘦质量有所减少。当老鼠还在吃这种食物的时候,行为测试就开始了。与cd喂养的小鼠相比,kd喂养的小鼠活性降低。在Morris水迷宫中,喂食kd的小鼠表现出路径效率下降,表明存在空间学习缺陷。在空间记忆和新物体识别记忆方面没有观察到差异。在情境恐惧和条件恐惧范式中,喂食kd的小鼠冻结行为增加。这些数据表明,生命早期暴露于KD会导致身体成分受损和长期认知变化。
The ketogenic diet (KD) is a non-pharmacological treatment for specific types of epilepsy. In addition, it has been shown to be effective in mitigating other neurologic disorders. The KD is also effective in reducing body mass, leading to an increase in use by the general population for weight loss. As the popularity of the clinical and general use of the KD has increased, it is important to develop adequate mouse models to better understand the effects of the KD in both normal and diseased states. Many times, the best outcome for disorders treatable with the KD would be achieved by commencing treatment in early life. Few studies have evaluated the cognitive effect of starting the KD in early life. To better understand these effects, male C57BL6/J mice were placed on a KD from postnatal day (P) 21 through young adulthood (~P90). KD-fed mice had increased blood ketone levels, reduced blood glucose, and reduced weight gain versus mice fed a control diet (CD). The weight loss in the KD-fed mice was not accompanied by a change in body fat percentage, suggesting that there was a loss of lean mass. Behavioral testing began on P60 while the mice were still on the diet. KD-fed mice were hypoactive with CD-fed mice. In the Morris water maze, KD-fed mice showed decreased path efficiency, suggesting a spatial learning deficits. No differences were observed in spatial memory or in novel object recognition memory. In a contextual and conditioned fear paradigm, the KD-fed mice had an increase in freezing behavior. These data suggest that early-life exposure to a KD leads to impaired body composition and long-term cognitive changes.
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发表时间: 1973-01-01
影响因子: 15.9
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