MADORE, Charlotte; LEYROLLE, Quentin; MOREL, Lydie; GREENHALGH, Andrew D.; LACABANNE, Chloe; BOSCH BOUJU, Clementine; BOUREL, Julien; THOMAZEAU, Aurore; HOPPERTON, K. E.; BECCARI, Sol; SERE, Alexandra; AUBERT, Agnes; DE SMEDT-PEYRUSSE, Veronique; LECOURS, C.; BISHT, K.; FOURGEAUD, L.; GREGOIRE, S.; BRETILLON, Lionel; GRANT, N. J.; BADAUT, Jerome; GRESSENS, P.; SIERRA, A.; BUTOVSKY, O.; TREMBLAY, Marie-Eve; BAZINET, Richard P.; JOFFRE, Corinne; NADJAR, Agnes; LAYE, Sophie

doi:10.1101/744136

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MADORE, Charlotte
Nutrition et Neurobiologie intégrée [NutriNeuro]

LEYROLLE, Quentin
Nutrition et Neurobiologie intégrée [NutriNeuro]

MOREL, Lydie
Nutrition et Neurobiologie intégrée [NutriNeuro]

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2021

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Omega-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 refinement via 12-HETE pathway in the developing brain.< Réduire

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Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

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