Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment
Neuropsychopharmacol. 2015-05-07; 40(12): 2774-2787
DOI: 10.1038/npp.2015.127
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1. Neuropsychopharmacology. 2015 Nov;40(12):2774-87. doi: 10.1038/npp.2015.127. Epub
2015 May 7.
Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced
Spatial Memory Impairment.
Delpech JC(1)(2), Thomazeau A(1)(2), Madore C(1)(2), Bosch-Bouju C(1)(2), Larrieu
T(1)(2), Lacabanne C(1)(2), Remus-Borel J(1)(2), Aubert A(1)(2), Joffre C(1)(2),
Nadjar A(1)(2), Layé S(1)(2).
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
(2)University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286,
Bordeaux, France.
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.
DOI: 10.1038/npp.2015.127
PMCID: PMC4864653
PMID: 25948102 [Indexed for MEDLINE]