School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China.
School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China.
Food Chem Toxicol. 2021 May;151:112105. doi: 10.1016/j.fct.2021.112105. Epub 2021 Mar 16.
To investigate the effects of alcohol intake on cognitive function and β-amyloid protein (Aβ) in APP/PS1 double-transgenic mice with Alzheimer's disease (AD). Sixty APP/PS1 transgenic male mice were randomized into seven groups: control group, 0.5% alcohol group, 1% alcohol group, 2% alcohol group, 3% alcohol group, and 4% alcohol group, with 10 non-transgenic B6C3F1 mice of the same genetic background as the negative control group. All mice were pair-fed a liquid diet containing alcohol before assessment of learning and memory using the Y-maze test, and of Aβ content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of Aβ, Aβ, and β-amyloid precursor protein (β-APP) in the cerebral cortex. 3%, and 4% alcohol intake significantly impaired the learning and memory abilities. 2%, 3%, and 4% alcohol groups indicated a remarkable change in Aβ content, α-secretase and γ-secretase activities in the hippocampus, and β-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in Aβ content, β-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in α-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in Aβ content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of Aβ, Aβ and β-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of Aβ, Aβ, β-APP, and BACE1 activity in the hippocampus, and γ-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of α-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and γ-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of β-APP decomposition-related enzymes, increase Aβ content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of Aβ and slow down AD progression.
为了研究酒精摄入对阿尔茨海默病（AD） APP/PS1 双转基因小鼠认知功能和 β-淀粉样蛋白（Aβ）的影响。将 60 只 APP/PS1 转基因雄性小鼠随机分为 7 组：对照组、0.5%酒精组、1%酒精组、2%酒精组、3%酒精组和 4%酒精组，以 10 只具有相同遗传背景的非转基因 B6C3F1 小鼠作为阴性对照组。在 Y 迷宫测试评估学习和记忆能力之前，所有小鼠均通过口饲含酒精的液体饮食喂养，之后检测它们的 Aβ 含量和相关酶活性。免疫组织化学检测大脑皮质中 Aβ、Aβ 和 β-淀粉样前体蛋白（β-APP）的表达。结果显示，3%和 4%酒精摄入显著损害学习和记忆能力。2%、3%和 4%酒精组的海马区 Aβ 含量、α-分泌酶和 γ-分泌酶活性及皮质区β-APP 均有显著变化；3%和 4%酒精组的海马或皮质区 Aβ 含量、β 位淀粉样蛋白裂解酶 1（BACE1）活性显著增加，α-分泌酶活性显著降低；2%和 3%酒精组海马或皮质区 Aβ 含量显著增加；2%、3%和 4%酒精组皮质区 Aβ、Aβ 和 β-APP 表达增加；1%酒精组海马区 Aβ、Aβ、β-APP 和 BACE1 活性及海马和皮质区 γ-分泌酶活性显著降低，1%酒精组海马区α-分泌酶活性显著升高。此外，0.5%酒精组海马区 BACE1 和 γ-分泌酶活性显著降低。长期摄入高剂量酒精可导致认知功能障碍，并提高β-APP 分解相关酶的活性，增加 Aβ 含量和沉积，引发 AD 进展，而长期摄入低剂量酒精可拮抗 Aβ 的过度产生，减缓 AD 进展。
