Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice
© 2019 Frontiers Media S.A.. All rights reserved. The causes and contributing factors of autism spectrum disorders (ASD) are poorly understood. One gene associated with increased risk for ASD is methylenetetrahydrofolate-reductase (MTHFR), which encodes a key enzyme in one carbon (C1) metabolism. Th...
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th-cmuir.6653943832-658442019-08-05T04:42:17Z Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice Ayelet Orenbuch Keren Fortis Siraphat Taesuwan Raz Yaffe Marie A. Caudill Hava M. Golan Neuroscience © 2019 Frontiers Media S.A.. All rights reserved. The causes and contributing factors of autism spectrum disorders (ASD) are poorly understood. One gene associated with increased risk for ASD is methylenetetrahydrofolate-reductase (MTHFR), which encodes a key enzyme in one carbon (C1) metabolism. The MTHFR 677C > T polymorphism reduces the efficiency of methyl group production with possible adverse downstream effects on gene expression. In this study, the effects of prenatal and/or postnatal diets enriched in C1 nutrients on ASD-like behavior were evaluated in Mthfr-deficient mice. Differences in intermediate pathways between the mice with and without ASD-like behaviors were tested. The findings indicate that maternal and offspring Mthfr deficiency increased the risk for an ASD-like phenotype in the offspring. The risk of ASD-like behavior was reduced in Mthfr-deficient mice supplemented with C1 nutrients prenatally. Specifically, among offspring of Mthfr+/-dams, prenatal diet supplementation was protective against ASD-like symptomatic behavior compared to the control diet with an odds ratio of 0.18 (CI:0.035, 0.970). Changes in major C1 metabolites, such as the ratios between betaine/choline and SAM/SAH in the cerebral-cortex, were associated with ASD-like behavior. Symptomatic mice presenting ASD-like behavior showed decreased levels of GABA pathway proteins such as GAD65/67 and VGAT and altered ratios of the glutamate receptor subunits GluR1/GluR2 in males and NR2A/NR2B in females. The altered ratios, in turn, favor receptor subunits with higher sensitivity to neuronal activity. Our study suggests that MTHFR deficiency can increase the risk of ASD-like behavior in mice and that prenatal dietary intervention focused on MTHFR genotypes can reduce the risk of ASD-like behavior. 2019-08-05T04:42:17Z 2019-08-05T04:42:17Z 2019-01-01 Journal 1662453X 16624548 2-s2.0-85068570220 10.3389/fnins.2019.00383 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068570220&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65844 |
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Neuroscience Ayelet Orenbuch Keren Fortis Siraphat Taesuwan Raz Yaffe Marie A. Caudill Hava M. Golan Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
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© 2019 Frontiers Media S.A.. All rights reserved. The causes and contributing factors of autism spectrum disorders (ASD) are poorly understood. One gene associated with increased risk for ASD is methylenetetrahydrofolate-reductase (MTHFR), which encodes a key enzyme in one carbon (C1) metabolism. The MTHFR 677C > T polymorphism reduces the efficiency of methyl group production with possible adverse downstream effects on gene expression. In this study, the effects of prenatal and/or postnatal diets enriched in C1 nutrients on ASD-like behavior were evaluated in Mthfr-deficient mice. Differences in intermediate pathways between the mice with and without ASD-like behaviors were tested. The findings indicate that maternal and offspring Mthfr deficiency increased the risk for an ASD-like phenotype in the offspring. The risk of ASD-like behavior was reduced in Mthfr-deficient mice supplemented with C1 nutrients prenatally. Specifically, among offspring of Mthfr+/-dams, prenatal diet supplementation was protective against ASD-like symptomatic behavior compared to the control diet with an odds ratio of 0.18 (CI:0.035, 0.970). Changes in major C1 metabolites, such as the ratios between betaine/choline and SAM/SAH in the cerebral-cortex, were associated with ASD-like behavior. Symptomatic mice presenting ASD-like behavior showed decreased levels of GABA pathway proteins such as GAD65/67 and VGAT and altered ratios of the glutamate receptor subunits GluR1/GluR2 in males and NR2A/NR2B in females. The altered ratios, in turn, favor receptor subunits with higher sensitivity to neuronal activity. Our study suggests that MTHFR deficiency can increase the risk of ASD-like behavior in mice and that prenatal dietary intervention focused on MTHFR genotypes can reduce the risk of ASD-like behavior. |
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Ayelet Orenbuch Keren Fortis Siraphat Taesuwan Raz Yaffe Marie A. Caudill Hava M. Golan |
author_facet |
Ayelet Orenbuch Keren Fortis Siraphat Taesuwan Raz Yaffe Marie A. Caudill Hava M. Golan |
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Ayelet Orenbuch |
title |
Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
title_short |
Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
title_full |
Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
title_fullStr |
Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
title_full_unstemmed |
Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
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prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice |
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2019 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068570220&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65844 |
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