Astaxanthin alleviates ganglioside metabolism disorder in the cortex of Alzheimer's disease mice

The present study analyzed the amelioration effect and mechanism of two kinds of astaxanthin (AST), including free-AST (F-AST) and docosahexaenoic acid-acylated AST monoester (AST-DHA), on ganglioside (GLS) metabolism in the cortex of APP/PS1 mice using the LC-MS strategy in combination with molecular biology. Water maze and immunohistochemical experiments demonstrated that AST significantly improved the cognitive level of APP/PS1 mice and reduced A beta deposition in the cortex. After the dietary intake of AST, the composition and level of 84 GLS molecular species in the mouse cortex were determined using the LC-MS strategy. The results showed that the total GLS was reduced, most complex GLS was decreased, and simple GLS (GM(3) and GM(1a)) was increased in the APP/PS1 mouse cortex. Notably, F-AST mainly regulated complex GLS (p < 0.001), whereas AST-DHA primarily reacted with simple GLS (p < 0.001). OAc-GQ(1a)(38:1), OAc-GQ(1a)(36:1), GD(1a)(36:1), and GM(3)(38:1) decreased 3.73, 2.31, and 2.29-fold and increased 3.54-fold, respectively, and were identified as potential AD biomarkers in the cortices of APP/PS1 mice. Additionally, the AST diet significantly upregulated the mRNA expression of GLS synthesizing genes (st3gal5, st8sia1, b3galt4, st3fal2, and soat) and siae (p < 0.05) and down-regulated that of the GLS catabolizing gene hexa (p < 0.01). In conclusion, improving GLS homeostasis in the AD mouse cortex might be a critical pathway to explain the AD-preventing effect of AST.