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

Brain Behav Immun. 2014 Oct;41:22-31. doi: 10.1016/j.bbi.2014.03.021. Epub 2014 Apr 13.


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.

Keywords: Brain development; DHA; M1/M2 phenotype; Microglia; Two-photon imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology*
  • Cell Count
  • Cell Movement
  • Cerebral Cortex / chemistry
  • Crosses, Genetic
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • 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
  • Lipids / deficiency*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • 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*
  • Sunflower Oil


  • Cytokines
  • Dietary Fats
  • Fatty Acids, Omega-3
  • Fish Oils
  • Lipids
  • Nerve Tissue Proteins
  • Plant Oils
  • Sunflower Oil