Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain
| Autor: | Sol Beccari, Charlotte Madore, Amanda Sierra, Oleg Butovsky, Stéphane Grégoire, Pierre Gressens, Kanchan Bisht, V. De Smedt-Peyrusse, K.E. Hopperton, Lawrence Fourgeaud, Sophie Layé, Corinne Joffre, Richard P. Bazinet, Agnès Nadjar, Lionel Morel, C. Lacabanne, J. Bourel, A. Sere, Jean-Christophe Delpech, Lionel Bretillon, Andrew D. Greenhalgh, Aurore Thomazeau, Clémentine Bosch-Bouju, Agnès Aubert, Quentin Leyrolle, N. J. Grant, Cynthia Lecours, Marie-Ève Tremblay, J. Badaut |
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| Přispěvatelé: | Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Admin, Oskar, BLANC - Dépression et Nutrition - - MoodFood2012 - ANR-12-BSV4-0025 - BLANC - VALID, Bordeaux Region Aquitaine Initiative for Neuroscience - - BRAIN2010 - ANR-10-LABX-0043 - LABX - VALID, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
2. Zero hunger
chemistry.chemical_classification 0303 health sciences medicine.medical_specialty biology Offspring Dietary intake Phagocytosis Hippocampus Hippocampal formation Synapse 03 medical and health sciences Lipoxygenase 0302 clinical medicine Endocrinology chemistry Internal medicine medicine biology.protein lipids (amino acids peptides and proteins) [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] 030217 neurology & neurosurgery 030304 developmental biology Polyunsaturated fatty acid |
| Popis: | SUMMARYOmega-3 fatty acids (n-3 polyunsaturated 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 epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.One Sentence SummaryLow maternal omega-3 fatty acids intake impairs microglia-mediated synaptic refinementvia12-HETE pathway in the developing brain. |
| Databáze: | OpenAIRE |
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