Blueberry extracts antagonize Aβ 25–35 neurotoxicity and exert a neuroprotective effect through MEK-ERK-BDNF/UCH-L1 signaling pathway in rat and mouse hippocampus

作者：Long Tan, Han Zhang, Haiqiang Li, Shoudan Sun, Quanjun Lyu, Yugang Jiang · 发表于：Nutritional Neuroscience · 年份：2023 · DOI：10.1080/1028415x.2023.2252640 · 被引用次数：6 · 研究领域：Alzheimer's disease research and treatments、Bioactive Compounds in Plants、Cholinesterase and Neurodegenerative Diseases

BACKGROUND: The neuroprotective potential of blueberry (BB) extracts against Alzheimer's disease (AD) has been previously hinted at, while its exact mechanism has remained largely enigmatic. OBJECTIVE: Our study endeavored to unravel the impacts and mechanisms by which BB extracts ameliorated the learning and memory prowess of AD-afflicted mice, with a specific focus on the MEK-ERK pathway. METHODS: We employed 3-month-old APP/PS1 transgenic mice and stratified them into three distinct groups: AD+BB, AD, and control (CT). The Morris Water Maze Test (MWMT) was then administered to gauge their learning and memory faculties. In vitro experiments were executed on Aβ25-35-afflicted rat hippocampal neurons, which were subsequently treated with varying concentrations of BB extracts. We then assessed the expression levels of genes and proteins integral to the MEK-ERKBDNF/UCH-L1 pathway. RESULTS: The data showed that the AD mice demonstrated compromised learning and memory faculties in MWMT. However, the AD+BB cohort showcased marked improvements in performance. Furthermore, in the AD subset, significant elevations in the expressions of MEK2 and ERK1/2 were observed, both at the mRNA and protein levels. Conversely, UCH-L1 mRNA expressions exhibited a decline, while BDNF expressions surged significantly. However, post BB extract treatment, the expressions of MEK2 and ERK1/2 were subdued, with UCH-L1 and BDNF mRNA expressions reverting to control levels. CONCLUSIONS: Our findings propou...