Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aβ degradation and inhibiting tau hyperphosphorylation.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aβ degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aβ40 and Aβ42 in serum, cortex, and hippocampus, and Aβ-related scavenging enzymes, phosphorylated GSK3β and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aβ deposition in their serum, cortex, and hippocampus. AS significantly increased Aβ degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3β, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aβ degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3β.