RESUMO
AIMS: Several lines of evidence suggest that the endocannabinoid system is involved in the regulation of glial activity. Enhanced levels of the endocannabinoid N-arachidonoyl ethanolamine (AEA, also referred to as anandamide) as well as non-cannabinoid lipids like palmitoylethanolamine (PEA) due to genetic deletion or pharmacologic blockade of its degrading enzyme fatty acid amide hydrolase (FAAH) reduced neuroinflammatory changes in models of neurodegeneration. Now we addressed the question if genetic deletion of FAAH also influences age-related neuroinflammation. MAIN METHODS: To answer this question we compared the number and size of microglia in young and old wild-type and FAAH(-/-) mice and analysed the distribution of microglia sizes in the four groups. Additionally, we analysed IL-6 and IL-1ß levels with ELISA and astrocyte activities as ratio of GFAP-positive areas in the hippocampus. KEY FINDINGS: Ageing was associated with an increased number and activity of microglia, elevated IL-6 and IL-1ß levels and enhanced area covered by astrocytes in wild-type animals. Unexpectedly, in FAAH(-/-) animals the number of microglia and the ratio of activated microglia and IL-1ß level were already higher in young animals than in age-matched wild-type controls. There was no further age-related increase in these inflammation markers in the knockout line. SIGNIFICANCE: Our results suggest that AEA is involved in the regulation of microglia activity. Life-long elevation of AEA levels disturbs microglial regulation and leads to pro-inflammatory changes.
