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Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis

The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving m...

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Autores principales: Chen, Siwei, Alhassen, Wedad, Yoshimura, Ryan, De Silva, Angele, Abbott, Geoffrey W., Baldi, Pierre, Alachkar, Amal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393105/
https://www.ncbi.nlm.nih.gov/pubmed/32732995
http://dx.doi.org/10.1038/s42003-020-01124-8
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author Chen, Siwei
Alhassen, Wedad
Yoshimura, Ryan
De Silva, Angele
Abbott, Geoffrey W.
Baldi, Pierre
Alachkar, Amal
author_facet Chen, Siwei
Alhassen, Wedad
Yoshimura, Ryan
De Silva, Angele
Abbott, Geoffrey W.
Baldi, Pierre
Alachkar, Amal
author_sort Chen, Siwei
collection PubMed
description The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving mediate these effects is, however, unknown. Here, we show that the behavioral deficits of MET are independent of the early life mother-infant interaction. We also show that MET produces in early life profound changes in the brain C1 pathway components as well as glutamate transmission, mitochondrial function, and lipid metabolism. Bioinformatics analysis integrating metabolomics and transcriptomic data reveal dysregulations of glutamate transmission and lipid metabolism, and identify perturbed pathways of methylation and redox reactions. Our transcriptomics Linkage analysis of MET mice and schizophrenia subjects reveals master genes involved in inflammation and myelination. Finally, we identify potential metabolites as early biomarkers for neurodevelopmental defects and suggest therapeutic targets for schizophrenia.
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spelling pubmed-73931052020-08-12 Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis Chen, Siwei Alhassen, Wedad Yoshimura, Ryan De Silva, Angele Abbott, Geoffrey W. Baldi, Pierre Alachkar, Amal Commun Biol Article The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving mediate these effects is, however, unknown. Here, we show that the behavioral deficits of MET are independent of the early life mother-infant interaction. We also show that MET produces in early life profound changes in the brain C1 pathway components as well as glutamate transmission, mitochondrial function, and lipid metabolism. Bioinformatics analysis integrating metabolomics and transcriptomic data reveal dysregulations of glutamate transmission and lipid metabolism, and identify perturbed pathways of methylation and redox reactions. Our transcriptomics Linkage analysis of MET mice and schizophrenia subjects reveals master genes involved in inflammation and myelination. Finally, we identify potential metabolites as early biomarkers for neurodevelopmental defects and suggest therapeutic targets for schizophrenia. Nature Publishing Group UK 2020-07-30 /pmc/articles/PMC7393105/ /pubmed/32732995 http://dx.doi.org/10.1038/s42003-020-01124-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Siwei
Alhassen, Wedad
Yoshimura, Ryan
De Silva, Angele
Abbott, Geoffrey W.
Baldi, Pierre
Alachkar, Amal
Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title_full Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title_fullStr Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title_full_unstemmed Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title_short Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
title_sort metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393105/
https://www.ncbi.nlm.nih.gov/pubmed/32732995
http://dx.doi.org/10.1038/s42003-020-01124-8
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