Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation.
Brain, Behavior, and Immunity. 2018-10-01; 73: 427-440
DOI: 10.1016/j.bbi.2018.06.004
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Labrousse VF(1), Leyrolle Q(2), Amadieu C(1), Aubert A(1), Sere A(1), Coutureau
E(3), Grégoire S(4), Bretillon L(4), Pallet V(1), Gressens P(5), Joffre C(1),
Nadjar A(6), Layé S(7).
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux,
France.
(2)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux,
France; PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, F-75019
Paris, France.
(3)Centre National de la Recherche Scientifique, Institut de Neurosciences
Cognitives et Intégratives d’Aquitaine, Uité Mixte de Recherche 5287, 33076
Bordeaux, France; Université de Bordeaux, Institut de Neurosciences Cognitives et
Intégratives d’Aquitaine, 33076 Bordeaux, France.
(4)Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRA,
Université Bourgogne Franche-Comté, Dijon, France.
(5)PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, 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, United Kingdom.
(6)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux,
France. Electronic address: .
(7)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux,
France. Electronic address: .
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 for the apparition of
neurodevelopmental disorders.
Copyright © 2018 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2018.06.004
PMID: 29879442