CPEB1,a novel risk gene in recent-onset schizophrenia,contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1  

作　　者：Ya-Ru Xia Xiao-Cui Wei Wen-Shi Li Qiu-Jin Yan Xiu-Lin Wu Wei Yao Xu-Hang Li Fan Zhu 

机构地区：[1]State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy&Immunology,Department of Medical Microbiology,School of Medicine,Wuhan University,Wuhan 430071,Hubei Province,China

出　　处：《World Journal of Psychiatry》2021年第11期1075-1094,共20页世界精神病学杂志

基　　金：Supported by the National Natural Science Foundation of China,No.81971943,No.81772196,No.31470264,No.81271820,No.30870789,and No.30300117;the Stanley Foundation of United States,No.06R-1366(for Zhu F);the Medical Science Advancement Program(Basic Medical Sciences)of Wuhan University,No.TFJC 2018002.

摘　　要：BACKGROUND Schizophrenia afflicts 1%of the world population.Clinical studies suggest that schizophrenia patients may have an imbalance of mitochondrial energy metabolism via inhibition of mitochondrial complex I activity.Moreover,recent studies have shown that ERVWE1 is also a risk factor for schizophrenia.Nevertheless,there is no available literature concerning the relationship between complex I deficits and ERVWE1 in schizophrenia.Identifying risk factors and blood-based biomarkers for schizophrenia may provide new guidelines for early interventions and prevention programs.AIM To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia.METHODS Quantitative polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay were used to detect differentially expressed risk factors in blood samples.Clinical statistical analyses were performed by median analyses and Mann-Whitney U analyses.Spearman’s rank correlation was applied to examine the correlation between different risk factors in blood samples.qPCR,western blot analysis,and luciferase assay were performed to confirm the relationship among ERVWE1,cytoplasmic polyadenylation element-binding protein 1(CPEB1),NADH dehydrogenase ubiquinone flavoprotein 2(NDUFV2),and NDUFV2 pseudogene(NDUFV2P1).The complex I enzyme activity microplate assay was carried out to evaluate the complex I activity induced by ERVWE1.RESULTS Herein,we reported decreasing levels of CPEB1 and NDUFV2 in schizophrenia patients.Further studies showed that ERVWE1 was negatively correlated with CPEB1 and NDUFV2 in schizophrenia.Moreover,NDUFV2P1 was increased and demonstrated a significant positive correlation with ERVWE1 and a negative correlation with NDUFV2 in schizophrenia.In vitro experiments disclosed that ERVWE1 suppressed NDUFV2 expression and promoter activity by increasing NDUFV2P1 level.The luciferase assay revealed that ERVWE1 could enhance the promoter activity of NDUFV2P1.Additionally,ERVWE1 down

关 键 词：ERVWE1 CPEB1 NADH dehydrogenase ubiquinone flavoprotein 2 complex I PSEUDOGENE 

分 类 号：R749.3[医药卫生—神经病学与精神病学]