Icariin Ameliorates Alzheimer's Disease Pathology by Alleviating Myelin Injury in 3 x Tg-AD Mice

摘要

Alzheimer's disease (AD) is a neurodegenerative disease characterized by excessive deposition of beta amyloid (A beta), hyperphosphorylation of tau protein, and neuronal cell death. Recent studies have shown that myelin cell damage, which leads to cognitive dysfunction, occurs before AD-related pathological changes. Here, we examine the effect of icariin (ICA), a prenylated flavonol glycoside, in improving cognitive function in AD model mice. ICA has been reported to exhibit cardiovascular protective functions and antiaging effects. In this study, we used 3 x Tg-AD mice as an AD model. The Morris water maze and Y maze tests were performed to assess the learning and memory of the mice. Immunofluorescence analysis of A beta 1-42 deposition and myelin basic protein (MBP) expression in the mouse hippocampus was performed. Tau protein phosphorylation and MBP protein expression in the hippocampus were further analyzed by Western blotting. Myelin damage in the mouse optic nerve was evaluated by electron microscopy, and LFB staining was performed to assess myelin morphology in the mouse corpus callosum. MBP, Mpp5, and Egr2 transcript levels were quantified by qPCR. We observed that ICA treatment improved the learning and memory of 3 x Tg-AD mice and reduced A beta deposition and tau protein phosphorylation in the hippocampus. Moreover, this treatment protocol increased myelin-related gene expression and reduced myelin damage.