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Metabolomic profiling on rat brain of prenatal malnutrition: implicated for oxidative stress and schizophrenia

  • Fei Xu
  • Xin Li
  • Weibo Niu
  • Gaini Ma
  • Qianqian Sun
  • Yan Bi
  • Zhenming Guo
  • Decheng Ren
  • Jiaxin Hu
  • Fan Yuan
  • Ruixue Yuan
  • Lei Shi
  • Xingwang Li
  • Tao Yu
  • Fengping Yang
  • Lin He
  • Xinzhi ZhaoEmail author
  • Guang HeEmail author
Original Article

Abstract

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring. All these abnormalities are highly consistent with the pathophysiology of schizophrenia. We developed a prenatal famine rat model by restricting daily diet of the pregnant rat to 50% of low protein diet. A metabolomics study of prefrontal cortex was performed to integrate GC-TOFMS and UPLC-QTOFMS. Thirteen controls and thirteen famine offspring were used to differentiate in PLS-DA (partial least squares-discriminate analysis) model. Furthermore, metabolic pathways and diseases were enriched via KEGG and HMDB databases, respectively. A total of 67 important metabolites were screened out according to the multivariate analysis. Schizophrenia was the most statistical significant disease (P = 0.0016) in our famine model. These metabolites were enriched in key metabolic pathways related to energy metabolism and glutamate metabolism. Based on these important metabolites, further discussion speculated famine group was characterized by higher level of oxidized damage compared to control group. We proposed that oxidative stress might be the pathogenesis of prenatal undernutrition which is induced schizophrenia.

Keywords

Schizophrenia Prenatal malnutrition Metabolic 

Notes

Acknowledgements

We appreciate the contribution of the members participating in this study. This work was supported by the National Key Research and Development Program (2016YFC0906400, 2016YFC1306700, 2016YFC0905000), the National Nature Science Foundation of China (81421061, 81361120389, 814018238), and the Shanghai Key Laboratory of Psychotic Disorders (13dz2260500).

Author’s contribution

HG and ZXZ conceptualized this experiment. LX analyzed data and provided ideas for this manuscript. XF wrote this paper. Others participated in the course of rats feeding.

Compliance with ethical standards

All the experimental procedures and protocols were complied with the National Institute of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee at Experimental Animal Center in Shanghai Jiao Tong University.

Conflict of interest

All authors have no conflicts of interest in this work.

Supplementary material

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11011_2019_468_MOESM2_ESM.xlsx (47 kb)
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Fei Xu
    • 1
    • 2
  • Xin Li
    • 1
    • 2
  • Weibo Niu
    • 1
    • 2
  • Gaini Ma
    • 1
    • 2
  • Qianqian Sun
    • 1
    • 2
  • Yan Bi
    • 1
    • 2
  • Zhenming Guo
    • 1
    • 2
  • Decheng Ren
    • 1
    • 2
  • Jiaxin Hu
    • 1
    • 2
  • Fan Yuan
    • 1
    • 2
  • Ruixue Yuan
    • 1
    • 2
  • Lei Shi
    • 1
    • 2
  • Xingwang Li
    • 1
    • 2
  • Tao Yu
    • 1
    • 2
  • Fengping Yang
    • 1
    • 2
  • Lin He
    • 1
    • 2
    • 3
  • Xinzhi Zhao
    • 4
    • 5
    Email author
  • Guang He
    • 1
    • 2
    Email author
  1. 1.Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education)Shanghai Jiao Tong UniversityShanghaiChina
  2. 2.Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research CenterShanghai Jiao Tong UniversityShanghaiChina
  3. 3.Shanghai Key Laboratory of Reproductive MedicineShanghai Jiao Tong UniversityShanghaiChina
  4. 4.Institute of Embryo-Fetal Original Adult Disease, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  5. 5.International Peace Maternity and Child Health Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina

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