Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

Neuropsychopharmacology. 2015 Nov;40(12):2774-87. doi: 10.1038/npp.2015.127. Epub 2015 May 7.


Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Corticosterone / blood
  • Cytokines / blood
  • Cytokines / genetics
  • Dendritic Spines / drug effects
  • Dendritic Spines / pathology
  • Dendritic Spines / ultrastructure
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / metabolism*
  • Gene Expression Regulation / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Inflammation / blood
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Lipopolysaccharides / toxicity
  • Long-Term Synaptic Depression / drug effects
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / etiology*
  • Memory Disorders / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neurons / pathology
  • Neurons / physiology
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Silver Staining


  • Cytokines
  • Fatty Acids, Omega-3
  • Lipopolysaccharides
  • Corticosterone