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Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodev...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704669/ https://www.ncbi.nlm.nih.gov/pubmed/33257673 http://dx.doi.org/10.1038/s41467-020-19861-z |
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author | Madore, C. Leyrolle, Q. Morel, L. Rossitto, M. Greenhalgh, A. D. Delpech, J. C. Martinat, M. Bosch-Bouju, C. Bourel, J. Rani, B. Lacabanne, C. Thomazeau, A. Hopperton, K. E. Beccari, S. Sere, A. Aubert, A. De Smedt-Peyrusse, V. Lecours, C. Bisht, K. Fourgeaud, L. Gregoire, S. Bretillon, L. Acar, N. Grant, N. J. Badaut, J. Gressens, P. Sierra, A. Butovsky, O. Tremblay, M. E. Bazinet, R. P. Joffre, C. Nadjar, A. Layé, S. |
author_facet | Madore, C. Leyrolle, Q. Morel, L. Rossitto, M. Greenhalgh, A. D. Delpech, J. C. Martinat, M. Bosch-Bouju, C. Bourel, J. Rani, B. Lacabanne, C. Thomazeau, A. Hopperton, K. E. Beccari, S. Sere, A. Aubert, A. De Smedt-Peyrusse, V. Lecours, C. Bisht, K. Fourgeaud, L. Gregoire, S. Bretillon, L. Acar, N. Grant, N. J. Badaut, J. Gressens, P. Sierra, A. Butovsky, O. Tremblay, M. E. Bazinet, R. P. Joffre, C. Nadjar, A. Layé, S. |
author_sort | Madore, C. |
collection | PubMed |
description | Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency. |
format | Online Article Text |
id | pubmed-7704669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77046692020-12-03 Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain Madore, C. Leyrolle, Q. Morel, L. Rossitto, M. Greenhalgh, A. D. Delpech, J. C. Martinat, M. Bosch-Bouju, C. Bourel, J. Rani, B. Lacabanne, C. Thomazeau, A. Hopperton, K. E. Beccari, S. Sere, A. Aubert, A. De Smedt-Peyrusse, V. Lecours, C. Bisht, K. Fourgeaud, L. Gregoire, S. Bretillon, L. Acar, N. Grant, N. J. Badaut, J. Gressens, P. Sierra, A. Butovsky, O. Tremblay, M. E. Bazinet, R. P. Joffre, C. Nadjar, A. Layé, S. Nat Commun Article Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency. Nature Publishing Group UK 2020-11-30 /pmc/articles/PMC7704669/ /pubmed/33257673 http://dx.doi.org/10.1038/s41467-020-19861-z 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 Madore, C. Leyrolle, Q. Morel, L. Rossitto, M. Greenhalgh, A. D. Delpech, J. C. Martinat, M. Bosch-Bouju, C. Bourel, J. Rani, B. Lacabanne, C. Thomazeau, A. Hopperton, K. E. Beccari, S. Sere, A. Aubert, A. De Smedt-Peyrusse, V. Lecours, C. Bisht, K. Fourgeaud, L. Gregoire, S. Bretillon, L. Acar, N. Grant, N. J. Badaut, J. Gressens, P. Sierra, A. Butovsky, O. Tremblay, M. E. Bazinet, R. P. Joffre, C. Nadjar, A. Layé, S. Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title | Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title_full | Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title_fullStr | Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title_full_unstemmed | Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title_short | Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
title_sort | essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704669/ https://www.ncbi.nlm.nih.gov/pubmed/33257673 http://dx.doi.org/10.1038/s41467-020-19861-z |
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