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

Abstract

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&#x3b2; 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 (GMand GM) was increased in the APP/PS1 mouse cortex. Notably, F-AST mainly regulated complex GLS (< 0.001), whereas AST-DHA primarily reacted with simple GLS (< 0.001). OAc-GQ(38:1), OAc-GQ(36:1), GD(36:1), and GM(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 (,,,, and) and(< 0.05) and down-regulated that of the GLS catabolizing gene(< 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.