TY - JOUR T1 - Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain JF - bioRxiv DO - 10.1101/744136 SP - 744136 AU - C. Madore AU - Q. Leyrolle AU - L. Morel AU - J.C. Delpech AU - A.D. Greenhalgh AU - C. Lacabanne AU - C. Bosch-Bouju AU - J. Bourel AU - A. Thomazeau AU - K.E. Hopperton AU - S. Beccari AU - A. Sere AU - A. Aubert AU - V. De Smedt-Peyrusse AU - C. Lecours AU - K. Bisht AU - L. Fourgeaud AU - S. Gregoire AU - L. Bretillon AU - N. J. Grant AU - J. Badaut AU - P. Gressens AU - A. Sierra AU - O. Butovsky AU - M.E. Tremblay AU - R.P. Bazinet AU - C. Joffre AU - A. Nadjar AU - S. LayƩ Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/04/744136.abstract N2 - 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 Summary Low maternal omega-3 fatty acids intake impairs microglia-mediated synaptic refinement via 12-HETE pathway in the developing brain. ER -