| First Author | Delpech JC | Year | 2015 |
| Journal | Neuropsychopharmacology | Volume | 40 |
| Issue | 3 | Pages | 525-36 |
| PubMed ID | 25228141 | Mgi Jnum | J:298879 |
| Mgi Id | MGI:6432972 | Doi | 10.1038/npp.2014.196 |
| Citation | Delpech JC, et al. (2015) Transgenic increase in n-3/n-6 fatty acid ratio protects against cognitive deficits induced by an immune challenge through decrease of neuroinflammation. Neuropsychopharmacology 40(3):525-36 |
| abstractText | 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. |
