Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes

• Published in: Brain, behavior, and immunity behavior, and immunity, 2014-10, Vol.41, p.22-31
• Main Authors: Madore, Charlotte, Nadjar, Agnès, Delpech, Jean-Christophe, Sere, A, Aubert, A, Portal, Céline, Joffre, Corinne, Layé, Sophie
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Brain - immunology; Brain development; Cell Count; Cell Movement; Cerebral Cortex - chemistry; Crosses, Genetic; Cytokines - biosynthesis; Cytokines - genetics; DHA; Dietary Fats - administration & dosage; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - analysis; Fatty Acids, Omega-3 - physiology; Female; Fish Oils; Gene Expression Regulation, Developmental; Hippocampus - immunology; Hippocampus - metabolism; Hippocampus - pathology; Immunity, Innate; Lactation; Life Sciences; Lipids - deficiency; M1/M2 phenotype; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - immunology; Microglia - physiology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neuroimmunomodulation; Neuronal Plasticity - genetics; Neuronal Plasticity - immunology; Plant Oils - administration & dosage; Pregnancy; Prenatal Exposure Delayed Effects; Psychiatry; Sunflower Oil; Two-photon imaging
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2014.03.021

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.