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Dietary lipids and microglia priming
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Edité par CCSD -
International audience. Growing number of studies highlight the link between food habits and the brain inflammatory response. In particular, the balance of n-3/n-6 polyunsaturated fatty acid (PUFA) intake may affect the synthesis and release of pro and anti-inflammatory factors by microglia. In support of this, decreased n-3 PUFA in the brain is associated to a higher expression of proinflammatory cytokine in response to inflammatory stimuli, and n-3 PUFA supplementation successfully decreases neuroinflammation. Decreased docosahexaenoic acid (DHA, 22:6n-3), the main long chain n-3 PUFA found in the brain could account for proinflammatory cytokine overproduction. DHA is converted from its precursor, α-linolenic acid (ALA, 18:3n-3), which is provided by the diet. However, the mechanisms underlying the susceptibility of microglia from n-3 deprived mice to overproduce proinflammatory factors remain to be determined. DHA decrease in the brain is accompanied by an increase in endocannabinoid (eCB) synthesis together with a desensitization of its receptor CB1. We hypothesized that dietary n-3 PUFA deficiency leads to changes in microglia activity in the brain with neurobehavioral outcomes. To test this hypothesis, mice were submitted to a diet deficient or not in ALA throughout gestation and lactation and microglia morphology, phenotype and function were studied at post-natal day (PND) 21 and at adulthood. DHA was significantly decreased in the phospholipids of ALA-deprived microglia membrane. As a consequence, phagocytic microglia number dramatically increased, dendritic arborisation is impaired in discrete brain structures involved in cognition and spatial memory is altered. In addition, the administration of lipopolysaccharide (LPS), a gram-negative bacteria endotoxin, to n-3 deprived mice over activated microglia. The consequences of microglia hyper activation are exaggerated production of proinflammatory factors such as cytokines. We will discuss the current understanding of n-3 deprivation-induced microglia priming and the consequences on brain functions. In particular, the cause of this amplified activation may be related to the impairment of negative regulatory system such as eCB.
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