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| Status |
Public on Jul 15, 2020 |
| Title |
Metabolomic and Transcriptomic Signatures of Prenatal Excessive Methionine in Mice Support Nature Rather than Nurture in the Pathogenesis and Therapy of Schizophrenia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Abstract: 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 new therapeutic targets for schizophrenia.
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| Overall design |
Saline pup brain and Methionine pup brain
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| Contributor(s) |
Chen S, Alhassen W, Yoshimura R, De Silva A, Abbott GW, Baldi P, Alachkar A |
| Citation(s) |
32732995 |
| Submission date |
Jun 24, 2020 |
| Last update date |
Aug 24, 2020 |
| Contact name |
Amal Alachkar |
| Organization name |
University of California Irvine
|
| Street address |
355 Med Surge II
|
| City |
Irvine, CA |
| ZIP/Postal code |
92697 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA641703 |
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