title: AMPK activation prevents prenatal stress-induced cognitive impairment: modulation of mitochondrial content and oxidative stress.
abstract: 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 mitochondrial 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.
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Adi
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.affiliation: Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, FIST, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China. Electronic address: zhfeng@mail.xjtu.edu.cn.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D003071:Cognition / Q000502:physiology; D060825:Cognitive Dysfunction / Q000517:prevention & control* / Q000523:psychology; D004789:Enzyme Activation; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013267:Stilbenes; D055372:AMP-Activated Protein Kinases; D005978:Glutathione; D000077185:Resveratrol
keywords: AMPK; Cognitive function; Mitochondrial biogenesis; Oxidative stress; Prenatal stress; Resveratrol