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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.

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1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
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.

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