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人工饲养通过作用于脑发育过程中的促凋亡信号分子来抑制凋亡细胞死亡:替代舔舐部分逆转了这些效应。

Artificial rearing inhibits apoptotic cell death through action on pro-apoptotic signaling molecules during brain development: replacement licking partially reverses these effects.

机构信息

Department of Psychology University of Toronto at Mississauga 3359 Mississauga Road North Mississauga, Ontario, Canada L5L1C6.

出版信息

Brain Res. 2010 Aug 12;1348:10-20. doi: 10.1016/j.brainres.2010.05.092. Epub 2010 Jun 8.

Abstract

Early life stress associated with being reared without mother, siblings, and nest affects the formation of neuronal networks during rat development. Prior work shows that in comparison to mother-reared male rats, artificial rearing results in elevated numbers of neurons in adulthood and reduced apoptosis during the first postnatal week. Replacement with stroking stimulation, designed to simulate mothers' licking, reversed these effects in most brain areas. The present communication explored the effects of early rearing manipulations on signaling proteins. Male rats were reared until postnatal day 7 either in an artificial-feeding paradigm (AR) or with their mothers (MR). AR animals received different amounts of maternal-like stimulation using a soft paintbrush. Brains were extracted and prepared for molecular assays of 1) apoptosis and 2) pro and anti-apoptotic proteins on day 7 of postnatal life. Results showed that stimulation of the AR pups reversed the effects of artificial rearing on apoptosis in a dose dependent manner; low and very high levels of stimulation were without effect whereas moderate levels of stimulation produced effects on apoptosis similar to effects seen in mother-reared controls. Moreover, this artificial rearing effect and the pattern of reversal with stroking were also found for levels of pro-apoptotic Bax protein, the ratio of Bax/Bcl-2 and levels of activated caspase-3 which we believe mediates programmed cell death.

摘要

早期生活压力与没有母亲、兄弟姐妹和巢穴的养育有关,会影响大鼠发育过程中神经网络的形成。先前的工作表明,与由母亲养育的雄性大鼠相比,人工养育会导致成年后神经元数量增加,并且在出生后的第一周内细胞凋亡减少。用设计用来模拟母亲舔舐的抚摸刺激来替代,会使大多数大脑区域的这些影响逆转。本研究探讨了早期养育处理对信号蛋白的影响。雄性大鼠在出生后 7 天内要么在人工喂养范式(AR)中饲养,要么与母亲一起饲养(MR)。AR 动物使用软毛刷接受不同量的类似母亲的刺激。在出生后 7 天提取大脑并准备进行 1)凋亡和 2)促凋亡和抗凋亡蛋白的分子检测。结果表明,刺激 AR 幼仔以剂量依赖的方式逆转了人工养育对凋亡的影响;低水平和非常高水平的刺激均无影响,而中等水平的刺激对凋亡的影响与由母亲养育的对照组相似。此外,我们还发现,这种人工养育的影响以及与抚摸刺激的逆转模式,也存在于促凋亡 Bax 蛋白的水平、Bax/Bcl-2 的比例以及激活的 caspase-3 的水平上,我们认为这些蛋白介导了程序性细胞死亡。

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