Dietary Fish Hydrolysate Improves Memory Performance Through Microglial Signature Remodeling During Aging.
Brain aging is characterized by a chronic low-grade inflammation, which significantly impairs cognitive function. Microglial cells, the immunocompetent cells of the brain, present a different phenotype, switching from a homeostatic signature (M0) to a more reactive phenotype called "MGnD" (microglial neurodegenerative phenotype), leading to a high production of pro-inflammatory cytokines. Furthermore, microglial cells can be activated by age-induced gut dysbiosis through the vagus nerve or the modulation of the peripheral immune system. Nutrients, in particular n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides, display powerful immunomodulatory properties, and can thus prevent age-related cognitive decline. The objective of this study was to investigate the effects of n-3 LC-PUFAs and low molecular weight peptides contained in a marine by-product-derived hydrolysate on microglial phenotypes and intestinal permeability and their consequences on cognition in mice. We demonstrated that the hydrolysate supplementation for 8 weeks prevented short- and long-term memory decline during aging. These observations were linked to the modulation of microglial signature. Indeed, the hydrolysate supplementation promoted homeostatic microglial phenotype by increasing TGF-β1 expression and stimulated phagocytosis by increasing Clec7a expression. Moreover, the hydrolysate supplementation promoted anti-inflammatory intestinal pathway and tended to prevent intestinal permeability alteration occurring during aging. Therefore, the fish hydrolysate appears as an interesting candidate to prevent cognitive decline during aging.
['Chataigner|Mathilde|M|', 'Lucas|Céline|C|', 'Di Miceli|Mathieu|M|', 'Pallet|Véronique|V|', 'Laye|Sophie|S|', 'Mehaignerie|Alexis|A|', 'Bouvret|Elodie|E|', 'Dinel|Anne-Laure|AL|', 'Joffre|Corinne|C|']
hydrolysate memory aging low molecular weight peptides cognitive decline microglia n-3 long chain PUFA