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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.

Author information

1
1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
2
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

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
PMCID:
PMC4289942
DOI:
10.1038/npp.2014.196
[Indexed for MEDLINE]
Free PMC Article

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