Metabolomic profiling on rat brain of prenatal malnutrition: implicated for oxidative stress and schizophrenia
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.
KeywordsSchizophrenia Prenatal malnutrition Metabolic
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).
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.
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