We investigate the effects of a chronic treatment with an endogenous lipid mediator palmitoylethanolamide on the onset and progression of AD in 3xTg-AD mice. Behavioural tests showed improvements in learning and memory, and in both the depressive and anhedonia-like phenotype in PEA-treated 3×Tg-AD mice. MRI/MRS in vivo analysis, microdialysis and western blot, RT-PCR, and immunofluorescence show that PEA normalizes astrocytic function, rebalances glutamatergic transmission, and restrains neuroinflammation. The efficacy of PEA is particularly potent in younger mice, suggesting its potential as an early treatment.
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