Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex
Abstract Previous reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at t...
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| Format: | Article |
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Nature Portfolio
2023-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05492-9 |
| _version_ | 1797630018186117120 |
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| author | Lyvin Tat Noemi Cannizzaro Zachary Schaaf Shailaja Racherla Teodoro Bottiglieri Ralph Green Konstantinos S. Zarbalis |
| author_facet | Lyvin Tat Noemi Cannizzaro Zachary Schaaf Shailaja Racherla Teodoro Bottiglieri Ralph Green Konstantinos S. Zarbalis |
| author_sort | Lyvin Tat |
| collection | DOAJ |
| description | Abstract Previous reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at the cellular level of either deficient or excessive FA supply by comparably reducing dendritic arborization of cortical projection neurons. Here, we report that excessive amounts of FA decrease arborization of deep layer projection neurons, but not upper layer neurons and that reduced complexity of deep layer neurons is not observed when folic acid is replaced by folinic acid, a stable reduced form of folate. In addition, deficiency of B12, a vitamin that critically regulates folate metabolism, causes even more marked decreases in neuronal arborization in both deep and upper layer neurons and particularly in combination with FA excess. Furthermore, both FA excess and B12 deficiency affect synaptic density and morphology. Our findings point to neurodevelopmental risks associated with insufficient amounts of prenatal B12, particularly in association with high levels of FA intake, suggesting that the neurodevelopmental program is sensitive to an imbalance in the status of these interacting micronutrients. |
| first_indexed | 2024-03-11T11:02:08Z |
| format | Article |
| id | doaj.art-554deb412b694ff3b060f1085f0acc64 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-11T11:02:08Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-554deb412b694ff3b060f1085f0acc642023-11-12T12:27:02ZengNature PortfolioCommunications Biology2399-36422023-11-016111210.1038/s42003-023-05492-9Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortexLyvin Tat0Noemi Cannizzaro1Zachary Schaaf2Shailaja Racherla3Teodoro Bottiglieri4Ralph Green5Konstantinos S. Zarbalis6Department of Pathology and Laboratory Medicine, University of CaliforniaDepartment of Pathology and Laboratory Medicine, University of CaliforniaDepartment of Pathology and Laboratory Medicine, University of CaliforniaDepartment of Pathology and Laboratory Medicine, University of CaliforniaBaylor Scott & White Research Institute, Center of MetabolomicsDepartment of Pathology and Laboratory Medicine, University of CaliforniaDepartment of Pathology and Laboratory Medicine, University of CaliforniaAbstract Previous reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at the cellular level of either deficient or excessive FA supply by comparably reducing dendritic arborization of cortical projection neurons. Here, we report that excessive amounts of FA decrease arborization of deep layer projection neurons, but not upper layer neurons and that reduced complexity of deep layer neurons is not observed when folic acid is replaced by folinic acid, a stable reduced form of folate. In addition, deficiency of B12, a vitamin that critically regulates folate metabolism, causes even more marked decreases in neuronal arborization in both deep and upper layer neurons and particularly in combination with FA excess. Furthermore, both FA excess and B12 deficiency affect synaptic density and morphology. Our findings point to neurodevelopmental risks associated with insufficient amounts of prenatal B12, particularly in association with high levels of FA intake, suggesting that the neurodevelopmental program is sensitive to an imbalance in the status of these interacting micronutrients.https://doi.org/10.1038/s42003-023-05492-9 |
| spellingShingle | Lyvin Tat Noemi Cannizzaro Zachary Schaaf Shailaja Racherla Teodoro Bottiglieri Ralph Green Konstantinos S. Zarbalis Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex Communications Biology |
| title | Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| title_full | Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| title_fullStr | Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| title_full_unstemmed | Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| title_short | Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| title_sort | prenatal folic acid and vitamin b12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex |
| url | https://doi.org/10.1038/s42003-023-05492-9 |
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