Prenatal Nutritional Deficiency Reprogrammed Postnatal Gene Expression in Mammal Brains: Implications for Schizophrenia

Jiawei Xu, Guang He, Jingde Zhu, Xinyao Zhou, David St Clair, Teng Wang, Yuqian Xiang, Qingzhu Zhao, Qinghe Xing, Yun Liu, Lei Wang, Qiaoli Li, Lin He, Xinzhi Zhao

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Epidemiological studies have identified prenatal exposure to famine as a risk factor for schizophrenia, and animal models of prenatal malnutrition display structural and functional brain abnormalities implicated in schizophrenia. Methods: The offspring of the RLP50 rat, a recently developed animal model of prenatal famine malnutrition exposure, was used to investigate the changes of gene expression and epigenetic modifications in the brain regions. Microarray gene expression analysis was carried out in the prefrontal cortex and the hippocampus from 8 RLP50 offspring rats and 8 controls. MBD-seq was used to test the changes in DNA methylation in hippocampus depending on prenatal malnutrition exposure. Results: In the prefrontal cortex, offspring of RLP50 exhibit differences in neurotransmitters and olfactory-associated gene expression. In the hippocampus, the differentially-expressed genes are related to synaptic function and transcription regulation. DNA methylome profiling of the hippocampus also shows widespread but systematic epigenetic changes; in most cases (87%) this involves hypermethylation. Remarkably, genes encoded for the plasma membrane are significantly enriched for changes in both gene expression and DNA methylome profiling screens (p = 2.37 × 10-9 and 5.36 × 10-9, respectively). Interestingly, Mecp2 and Slc2a1, two genes associated with cognitive impairment, show significant down-regulation, and Slc2a1 is hypermethylated in the hippocampus of the RLP50 offspring. Conclusions: Collectively, our results indicate that prenatal exposure to malnutrition leads to the reprogramming of postnatal brain gene expression and that the epigenetic modifications contribute to the reprogramming. The process may impair learning and memory ability and result in higher susceptibility to schizophrenia.

Original languageEnglish
Article numberpyu054
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number4
Early online date24 Jan 2015
DOIs
Publication statusPublished - Feb 2015

Keywords

  • DNA methylation
  • Hippocampus
  • Prefrontal cortex
  • Schizophrenia
  • Transcriptome

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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    Xu, J., He, G., Zhu, J., Zhou, X., Clair, D. S., Wang, T., Xiang, Y., Zhao, Q., Xing, Q., Liu, Y., Wang, L., Li, Q., He, L., & Zhao, X. (2015). Prenatal Nutritional Deficiency Reprogrammed Postnatal Gene Expression in Mammal Brains: Implications for Schizophrenia. International Journal of Neuropsychopharmacology, 18(4), [pyu054]. https://doi.org/10.1093/ijnp/pyu054