AMPK activation prevents prenatal stress-induced cognitive impairment: Modulation of mitochondrial content and oxidative stress
AMPK activation prevents prenatal stress-induced cognitive impairment: Modulation of mitochondrial content and oxidative stress
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AMPK 激活可预防产前应激引起的认知障碍：线粒体含量和氧化应激的调节。
DOI：
10.1016/j.freeradbiomed.2014.07.029
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发表时间：
2014-10-01
影响因子：
7.4
通讯作者：
Peng, Zhihui
中科院分区：
文献类型：
--
作者：
Cao, Ke;Zheng, Adi;Peng, Zhihui
产前应激诱导后代认知功能障碍，线粒体功能障碍和氧化应激被认为是密切相关的事件。在这项研究中，参与的AMP激活的蛋白激酶（AMPK）途径进行了调查。一种众所周知的激活剂，白藜芦醇（Res），用于诱导AMPK在SH-SY-5 Y细胞中的激活。在Res处理后观察到显著的线粒体生物发生和II相酶激活，伴随着蛋白质氧化和GSSG含量的降低，并且用化合物c抑制AMPK消除了Res的诱导作用。利用产前束缚应激（PRS）动物模型的进一步研究表明，母体补充Res可以激活雄性和雌性后代的大脑中的AMPK，PRS-induced线粒体损失的后代海马抑制Res母体补充剂。此外，Res激活了Nrf 2介导的II相酶，并减少了雄性和雌性后代中PRS诱导的氧化损伤。此外，PRS显着降低各种神经元标记物的mRNA水平，以及由此产生的后代的认知功能，基于自发交替性能和Morris水迷宫测试的结果，这是显着改善母体Res补充。我们的研究结果提供的证据表明，AMPK可以调节线粒体含量和II相酶的神经元细胞，这一过程可能在预防应激诱导的认知障碍中发挥重要作用。通过线粒体生物合成和Nrf 2途径的偶联，AMPK可以调节氧化应激，并成为治疗神经系统疾病的有希望的靶点。(C)2014爱思唯尔公司All rights reserved.
Prenatal stress induces cognitive functional impairment in offspring, an eventuality in which mitochondrial dysfunction and oxidative stress are believed to be closely involved. In this study, the involvement of the AMP-activated protein kinase (AMPK) pathway was investigated. A well-known activator, resveratrol (Res), was used to induce AMPK activation in SH-SY-5Y cells. Significant mitochondrial biogenesis and phase II enzyme activation, accompanied by decreased protein oxidation and GSSG content, were observed after Res treatment, and inhibition of AMPK with Compound c abolished the induction effects of Res. Further study utilizing a prenatal restraint stress (PRS) animal model indicated that maternal supplementation of Res may activate AMPK in the hippocampi of both male and female offspring, and that PRS-induced mitochondrial loss in the offspring hippocampus was inhibited by Res maternal supplementation. In addition, Res activated Nrf2-mediated phase II enzymes and reduced PRS-induced oxidative damage in both male and female offspring. Moreover, PRS markedly decreased mRNA levels of various neuron markers, as well as resultant offspring cognitive function, based on spontaneous alternation performance and Morris water maze tests, the results of, which were significantly improved by maternal Res supplementation. Our results provide evidence indicating that AMPK may modulate rnitochondrial content and phase II enzymes in neuronal cells, a process which may play an essential role in preventing PRS-induced cognitive impairment. Through the coupling of mitochondrial biogenesis and the Nrf2 pathway, AMPK may modulate oxidative stress and be a promising target against neurological disorders. (C) 2014 Elsevier Inc. All rights reserved.