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

Autor:	Madore C; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France.; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women´s Hospital, Harvard Medical School, Boston, MA, USA., Leyrolle Q; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France.; NeuroDiderot, Inserm, Université de Paris Diderot, F-75019, Paris, France., Morel L; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Rossitto M; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Greenhalgh AD; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Delpech JC; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Martinat M; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Bosch-Bouju C; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Bourel J; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Rani B; Department of Health Sciences, University of Florence, Florence, Italy., Lacabanne C; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Thomazeau A; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Hopperton KE; Department of Nutritional Sciences, University of Toronto, Toronto, ON, M5S 3E2, Canada., Beccari S; Achucarro Basque Center for Neuroscience, University of the Basque Country and Ikerbasque Foundation, 48940, Leioa, Spain., Sere A; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Aubert A; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., De Smedt-Peyrusse V; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Lecours C; Neurosciences Axis, CRCHU de Québec-Université Laval, Québec City, QC, Canada., Bisht K; Neurosciences Axis, CRCHU de Québec-Université Laval, Québec City, QC, Canada., Fourgeaud L; Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA., Gregoire S; Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Univ. Bourgogne Franche-Comté, F-21000, Dijon, France., Bretillon L; Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Univ. Bourgogne Franche-Comté, F-21000, Dijon, France., Acar N; Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Univ. Bourgogne Franche-Comté, F-21000, Dijon, France., Grant NJ; CNRS UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France., Badaut J; CNRS UMR5287, University of Bordeaux, Bordeaux, France., Gressens P; NeuroDiderot, Inserm, Université de Paris Diderot, F-75019, Paris, France.; Centre for the Developing Brain, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, SE1 7EH, UK., Sierra A; Achucarro Basque Center for Neuroscience, University of the Basque Country and Ikerbasque Foundation, 48940, Leioa, Spain., Butovsky O; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women´s Hospital, Harvard Medical School, Boston, MA, USA.; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Tremblay ME; Neurosciences Axis, CRCHU de Québec-Université Laval, Québec City, QC, Canada., Bazinet RP; Department of Nutritional Sciences, University of Toronto, Toronto, ON, M5S 3E2, Canada., Joffre C; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., Nadjar A; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France. agnes.nadjar@u-bordeaux.fr., Layé S; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France. sophie.laye@inrae.fr.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Nov 30; Vol. 11 (1), pp. 6133. Date of Electronic Publication: 2020 Nov 30.
DOI:	10.1038/s41467-020-19861-z
Abstrakt:	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.
Databáze:	MEDLINE
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