title: Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes.
abstract: Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations.
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Madore
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Nadjar
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Delpech
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Sere
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Aubert
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Portal
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Joffre
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France. Electronic address: sophie.laye@bordeaux.inra.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D002452:Cell Count; D002465:Cell Movement; D002540:Cerebral Cortex / Q000737:chemistry; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000032:analysis / Q000502:physiology*; D005260:Female; D005395:Fish Oils; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate; D007774:Lactation; D008055:Lipids / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D015213:Neuroimmunomodulation; D009473:Neuronal Plasticity / Q000235:genetics / Q000276:immunology*; D010938:Plant Oils / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D000074242:Sunflower Oil
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008055:Lipids; D009419:Nerve Tissue Proteins; D010938:Plant Oils; D000074242:Sunflower Oil
keywords: Brain development; DHA; M1/M2 phenotype; Microglia; Two-photon imaging