Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation

• Published in: Brain, behavior, and immunity behavior, and immunity, 2018-10, Vol.73, p.427-440
• Main Authors: Labrousse, V.F., Leyrolle, Q., Amadieu, C., Aubert, A., Sere, A, Coutureau, E., Grégoire, S., Bretillon, L., Pallet, V., Gressens, P., Joffre, C., Nadjar, A., Layé, S.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Behavior, Animal - drug effects; Brain - drug effects; Cytokines; Cytokines - drug effects; Dietary Supplements; Disease Models, Animal; Fatty Acids, Omega-3 - deficiency; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-6 - metabolism; Fatty Acids, Omega-6 - physiology; Female; Food and Nutrition; Inflammation - metabolism; Life Sciences; Lipopolysaccharides - pharmacology; LPS; Memory; Memory Disorders - metabolism; Memory Disorders - physiopathology; MIA; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Neurodevelopmental Disorders - etiology; Neurodevelopmental Disorders - metabolism; Neurons and Cognition; Omega-3; Pregnancy; Prenatal Exposure Delayed Effects - immunology; Prenatal Exposure Delayed Effects - metabolism; PUFA; Social Behavior; Spatial Memory - drug effects
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2018.06.004

•Maternal omega-3 deficiency has deleterious effects on pups’ brain development.•Maternal omega-3 deficiency alters fatty acid composition of the fetal and adult offspring brain.•Maternal omega-3 deficiency exacerbates maternal and fetal inflammation.•Maternal omega-3 deficiency induces spatial memory deficits in the adult offspring.•There is a strong negative correlation between brain content in omega-3 and cytokines production. Maternal immune activation (MIA) is a common environmental insult on the developing brain and represents a risk factor for neurodevelopmental disorders. Animal models of in utero inflammation further revealed a causal link between maternal inflammatory activation during pregnancy and behavioural impairment relevant to neurodevelopmental disorders in the offspring. Accumulating evidence point out that proinflammatory cytokines produced both in the maternal and fetal compartments are responsible for social, cognitive and emotional behavioral deficits in the offspring. Polyunsaturated fatty acids (PUFAs) are essential fatty acids with potent immunomodulatory activities. PUFAs and their bioactive derivatives can promote or inhibit many aspects of the immune and inflammatory response. PUFAs of the n-3 series (‘n-3 PUFAs’, also known as omega-3) exhibit anti-inflammatory/pro-resolution properties and promote immune functions, while PUFAs of the n-6 series (‘n-6 PUFAs’ or omega-6) favor pro-inflammatory responses. The present study aimed at providing insight into the effects of n-3 PUFAs on the consequences of MIA on brain development. We hypothesized that a reduction in n-3 PUFAs exacerbates both maternal and fetal inflammatory responses to MIA and later-life defects in memory in the offspring. Based on a lipopolysaccharide (LPS) model of MIA (LPS injection at embryonic day 17), we showed that n-3 PUFA deficiency 1) alters fatty acid composition of the fetal and adult offspring brain; 2) exacerbates maternal and fetal inflammatory processes with no significant alteration of microglia phenotype, and 3) induces spatial memory deficits in the adult offspring. We also showed a strong negative correlation between brain content in n-3 PUFA and cytokine production in MIA-exposed fetuses. Overall, our study is the first to address the deleterious effects of n-3 PUFA deficiency on brain lipid composition, inflammation and memory performances in MIA-exposed animals and indicates that it should be considered as a potent environmental risk factor f