Transgenic increase in n-3/n-6 fatty acid ratio protects against cognitive deficits induced by an immune challenge through decrease of neuroinflammation
Neuropsychopharmacol. 2014-08-05; 40(3): 525-536
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1. Neuropsychopharmacology. 2015 Feb;40(3):525-36. doi: 10.1038/npp.2014.196. Epub
2014 Aug 5.
Transgenic increase in n-3/n-6 fatty acid ratio protects against cognitive
deficits induced by an immune challenge through decrease of neuroinflammation.
Delpech JC(1), Madore C(1), Joffre C(1), Aubert A(1), Kang JX(2), Nadjar A(1),
(1)1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France 
Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
(2)Department of Medicine, Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA.
Polyunsaturated fatty acids (PUFAs) display immunomodulatory properties in the
brain, n-3 PUFAs being able to reduce inflammation whereas n-6 PUFAs are more
pro-inflammatory. It has been extensively demonstrated that exposure to a
peripheral immune challenge leads to the production and release of inflammatory
mediators in the brain in association with cognitive deficits. The question
arises whether n-3 PUFA supplementation could downregulate the brain inflammatory
response and subsequent cognitive alterations. In this study, we used a
genetically modified mouse line carrying the fat-1 gene from the roundworm
Caenorhabditis elegans, encoding an n-3 PUFA desaturase that catalyzes conversion
of n-6 into n-3 PUFA. Consequently, these mice display endogenously elevated n-3
PUFA tissue contents. Fat-1 mice or wild-type (WT) littermates were injected
peripherally with lipopolysaccharide (LPS), a bacterial endotoxin, to induce an
inflammatory episode. Our results showed that LPS altered differently the
phenotype of microglia and the expression of cytokines and chemokines in Fat-1
and WT mice. In Fat-1 mice, pro-inflammatory factors synthesis was lowered
compared with WT mice, whereas anti-inflammatory mechanisms were favored 24 h
after LPS treatment. Moreover, LPS injection impaired spatial memory in WT mice,
whereas interestingly, the Fat-1 mice showed normal cognitive performances. All
together, these data suggest that the central n-3 PUFA increase observed in Fat-1
mice modulated the brain innate immune system activity, leading to the protection
of animals against LPS-induced pro-inflammatory cytokine production and
subsequent spatial memory alteration.
PMID: 25228141 [Indexed for MEDLINE]