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Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE ◇ SSCI ◇ 自然指数

作者：
Xiumin Wang[a] * ; Jianping Lu[b] * ; Weiguo Xie[c] * ; Xiaoyun Lu[a] ; Yujie Liang[b] ; Min Li[c] ; Zichen Wang[b] ; Xiaodong Huang[c] ; Mingxi Tang[d] ; Donald W. Pfaff[a,e] ; Ya-Ping Tang[a,d,f] ; Paul Yao[a,b,c] ;
机构： [a]Joint Center of Translational Precision Medicine, Guangzhou Institute of Pediatrics, Guangzhou Women and Children Medical Center, 510623 Guangzhou,China [b]Department of Child Psychiatry, Kangning Hospital of Shenzhen, 518020 Shenzhen, People’s Republic of China [c]Institute of Rehabilitation Center,Tongren Hospital of Wuhan University, 430060 Wuhan, People’s Republic of China [d]Department of Pathology, Affiliated Hospital of Southwest MedicalUniversity, Luzhou, 646000 Sichuan, China [e]Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065 [f]Departmentof Imaging, Affiliated Hospital 3, Zhengzhou University, 450052 Zhengzhou, China
出处：
DOI： 10.1073/pnas.1912625116
ISSN：

关键词： autism spectrum disorders epigenetics oxidative stress maternal diabetes SOD2

摘要：
Epidemiological studies show that maternal diabetes is associated with an increased risk of autism spectrum disorders (ASDs), although the detailed mechanisms remain unclear. The present study aims to investigate the potential effect of maternal diabetes on autism-like behavior in offspring. The results of in vitro study showed that transient hyperglycemia induces persistent reactive oxygen species (ROS) generation with suppressed superoxide dismutase 2 (SOD2) expression. Additionally, we found that SOD2 suppression is due to oxidative stress-mediated histone methylation and the subsequent dissociation of early growth response 1 (Egr1) on the SOD2 promoter. Furthermore, in vivo rat experiments showed that maternal diabetes induces SOD2 suppression in the amygdala, resulting in autism-like behavior in offspring. SOD2 overexpression restores, while SOD2 knockdown mimics, this effect, indicating that oxidative stress and SOD2 expression play important roles in maternal diabetes-induced autism-like behavior in offspring, while prenatal and postnatal treatment using antioxidants permeable to the blood-brain barrier partly ameliorated this effect. We conclude that maternal diabetes induces autism-like behavior through hyperglycemia-mediated persistent oxidative stress and SOD2 suppression. Here we report a potential mechanism for maternal diabetes-induced ASD.

基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31671098, 81620108021, 81772097]; Natural Science Foundation of Hubei Province of ChinaNatural Science Foundation of Hubei Province [2016CFB473]; Key Scientific and Technology Project of Guangzhou City [201704020221]; Key Scientific and Technology Project of Guangdong Province [2018B030335001]; Shenzhen Science and Technology Innovation Committee [JCYJ20160429185235132]; Sanming Project of Medicine in Shenzhen [SZSM201612079]; Key Technology and Research Developmental Program (KTRDP) of Sichuan Province [14ZC0054]
语种：
外文
被引次数：
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中科院(CAS)分区：
出版当年[2018]版：
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2017]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

第一作者：
第一作者机构： [a]Joint Center of Translational Precision Medicine, Guangzhou Institute of Pediatrics, Guangzhou Women and Children Medical Center, 510623 Guangzhou,China
共同第一作者：
通讯作者：
通讯机构： [a]Joint Center of Translational Precision Medicine, Guangzhou Institute of Pediatrics, Guangzhou Women and Children Medical Center, 510623 Guangzhou,China [b]Department of Child Psychiatry, Kangning Hospital of Shenzhen, 518020 Shenzhen, People’s Republic of China [c]Institute of Rehabilitation Center,Tongren Hospital of Wuhan University, 430060 Wuhan, People’s Republic of China [d]Department of Pathology, Affiliated Hospital of Southwest MedicalUniversity, Luzhou, 646000 Sichuan, China [e]Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065 [f]Departmentof Imaging, Affiliated Hospital 3, Zhengzhou University, 450052 Zhengzhou, China
推荐引用方式(GB/T 7714)：
Xiumin Wang,Jianping Lu,Weiguo Xie,et al.Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2019,116(47):23743-23752.doi:10.1073/pnas.1912625116.
APA：
Xiumin Wang,Jianping Lu,Weiguo Xie,Xiaoyun Lu,Yujie Liang...&Paul Yao.(2019).Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116,(47)
MLA：
Xiumin Wang,et al."Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116..47(2019):23743-23752

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