Guangzhou Vocational and Technical University of Science and Technology, Guang Zhou, Guang Dong, China.
Department of Acupuncture and Moxibustion, Shangyou Hospital of Traditional Chinese Medicine, Ganzhou City, Jiangxi, China.
Bull Exp Biol Med. 2023 Jul;175(3):335-340. doi: 10.1007/s10517-023-05863-6. Epub 2023 Aug 11.
This study examined the effect of curcumin on pathological manifestations and clearance of amyloid β peptide (Aβ) in the hippocampus of 8-month-old transgenic APP/PS1 mice with inherent Alzheimer's disease. APP/PS1 mice and the age-matched wild-type controls were subjected to 3 behavioral tests: open field, new object recognition, and Morris water maze. Expression of Aβ, APP, CTF, BACE1, IDE, NEP, and LRP1 proteins in the extracted hippocampal tissue was evaluated by Western blotting. The distribution and the quantity of amyloid plaques and the spread of microglia in the hippocampus were determined by immunofluorescence. The contents of Aβ40 and Aβ42 in the hippocampus were assayed and analyzed on Simoa HD-1 analyzer. The proteins interacting with Aβ in the hippocampus of APP/PS1 mice were detected by co-immunoprecipitation. Curcumin significantly reduced motor hyperactivity in the open-field test, improved short-term recognition memory, spatial learning, and reference memory in APP/PS1 mice. In the hippocampus of APP/PS1 mice, curcumin significantly diminished the elevated Aβ levels and inhibited microglia proliferation. At the same time, curcumin had no effect on Aβ production, extracellular enzymatic hydrolysis, and LRP1-mediated outward transport, but enhanced Aβ clearance by activation of the intracellular ubiquitin-proteasome system and related peripheral mechanisms. Thus, curcumin improves the learning and memory abilities of APP/PS1 mice and reduces the pathological accumulation of Aβ in the brain.
本研究探讨了姜黄素对具有内在阿尔茨海默病的 8 月龄转 APP/PS1 基因小鼠海马中淀粉样β肽（Aβ）病理表现和清除的影响。APP/PS1 小鼠和年龄匹配的野生型对照进行了 3 项行为学测试：旷场、新物体识别和 Morris 水迷宫。通过 Western blot 评估提取的海马组织中 Aβ、APP、CTF、BACE1、IDE、NEP 和 LRP1 蛋白的表达。通过免疫荧光测定海马中淀粉样斑块的分布和数量以及小胶质细胞的扩散。通过 Simoa HD-1 分析仪检测和分析海马中 Aβ40 和 Aβ42 的含量。通过共免疫沉淀检测 APP/PS1 小鼠海马中与 Aβ 相互作用的蛋白质。姜黄素显著减少了 APP/PS1 小鼠旷场测试中的运动过度活跃，改善了其短期识别记忆、空间学习和参考记忆。在 APP/PS1 小鼠的海马中，姜黄素显著降低了升高的 Aβ 水平并抑制了小胶质细胞的增殖。同时，姜黄素对 Aβ 的产生、细胞外酶解以及 LRP1 介导的外向转运没有影响，但通过激活细胞内泛素-蛋白酶体系统和相关的外周机制增强了 Aβ 的清除。因此，姜黄素改善了 APP/PS1 小鼠的学习和记忆能力，并减少了大脑中 Aβ 的病理性积累。
