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Communication Dans Un Congrès Année : 2013

Dietary lipids and microglia priming

Résumé

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.

Dates et versions

hal-02747574 , version 1 (03-06-2020)

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Sophie Layé, Charlotte Madore, Jean-Christophe Delpech, Agnes Nadjar, Corinne Joffre. Dietary lipids and microglia priming. 11. European Meeting on Glial Cell Function in Health and Disease, Jul 2013, Berlin, Germany. ⟨10.1002/glia.22531⟩. ⟨hal-02747574⟩
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