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

C. Madore, et al.

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Received Date: 24th July 19

C. Madore, Q. Leyrolle, L. Morel, J.C. Delpech, A.D. Greenhalgh, C. Lacabanne, C. Bosch-Bouju, J. Bourel, A. Thomazeau, K.E. Hopperton, S. Beccari, A. Sere, A. Aubert, V. De Smedt-Peyrusse, C. Lecours, K. Bisht, L. Fourgeaud, S. Gregoire, L. Bretillon, N. J. Grant, J. Badaut, P. Gressens, A. Sierra, O. Butovsky, M.E. Tremblay, R.P. Bazinet, C. Joffre, A. Nadjar, S. Layé

Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) areessential 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 identifya molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our resultsshow 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.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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