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

C. Madore 1 Q. Leyrolle 1 L. Morel 1 M. Rossitto 1 A. Greenhalgh 1 J. Delpech 1 M. Martinat 1 C. Bosch-Bouju 1 J. Bourel 1 B. Rani 2 C. Lacabanne 1 A. Thomazeau 1 K. Hopperton 3 S. Beccari 4, 5 A. Sere 1 A. Aubert 1 V. de Smedt-Peyrusse 1 C. Lecours 6 K. Bisht 6 L. Fourgeaud 7 Stéphane Grégoire 8, 9 Lionel Brétillon 8, 9 Niyazi Acar 8, 9 N. Grant 10 J. Badaut 11 P. Gressens 12 A. Sierra 4, 5 O. Butovsky 13 M. Tremblay 6 R. Bazinet 3 Corinne Joffre 1 Agnès Nadjar 1 Sophie Layé 1, *
* Corresponding author
1 NutriNeur0 - Nutrition et Neurobiologie intégrée
2 Università degli Studi di Firenze = University of Florence [Firenze]
3 Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada
4 University of the Basque Country
5 Ikerbasque - Basque Foundation for Science
6 CRCHUQ - Centre de recherche du CHU de Québec-Université Laval
7 The Salk Institute for Biological Studies
8 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
9 UBFC - Université Bourgogne Franche-Comté [COMUE]
10 Cytologie et cytopatholgie neuronales CNRS UPR 3212
11 INCI - Institut des Neurosciences Cellulaires et Intégratives
12 NeuroDiderot (UMR_S_1141 / U1141) - Maladies neurodéveloppementales et neurovasculaires
13 BWH - Brigham & Women’s Hospital [Boston]
Abstract : 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.
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Journal articles
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https://hal.inrae.fr/hal-03047178
Contributor : Sabine Julien <>
Submitted on : Tuesday, December 8, 2020 - 5:24:58 PM
Last modification on : Friday, March 5, 2021 - 1:44:01 PM

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C. Madore, Q. Leyrolle, L. Morel, M. Rossitto, A. Greenhalgh, et al.. Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.6133. ⟨10.1038/s41467-020-19861-z⟩. ⟨hal-03047178⟩

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