Effects of Quercetin Intervention on Cognition Function in APP/PS1 Mice was Affected by Vitamin D Status.

SCOPE: To explore how quercetin will affect memory impairments in APP/PS1 mice under different vitamin D status.

METHODS AND RESULTS: APP/PS1 mice are divided into four groups, i.e., control (CON), low (LVD), medium, and high vitamin D supplemented with quercetin. During Morris Water Maze test, mice of the LVD group function best for improving cognitive function demonstrated by reduced latency to platform, and increased number of crossing and swimming distance in the target quadrant. Compared to the CON group, in both hippocampus and cortex, the LVD group has significant reduction in Aβ plaques, p-Tau at Ser396&Ser404, and neuroinflammation. In the hippocampus, BDNF is elevated, miR-26a and miR-125b is decreased, while miR-132 is increased in the LVD group. The LVD group demonstrates increased gut microbial diversity and elevated relative abundance of Glutamicibacter, Facklamia and Aerocorrus. In the hippocampus, p-Tau at ser396&404, GFAP, Ibα1, miR-26a, and miR-132 are negatively correlated with Aerococcus; and p-Tau at ser404 and Ibα1 are negatively correlated with Facklamia.

CONCLUSION: Quercetin is more efficacious for improving cognitive function under low vitamin D status. This might be owing to that interventions reduce Aβ plaques, tau phosphorylation, and neuroinflammation, upregulate BDNF, reduce miR-26a and miR-125b, increase miR-132, and elevate gut microbial diversity including Facklamia and Aerococcus.