Fang Guang, Shi Baoyan, Wu Kefeng, Chen Siyu, Gao Xiang, Xiao Sa, Kang Jing X, Li Wende, Huang Ren
a Guangdong Key Laboratory for Research and Development of Natural Drug , Guangdong Medical University , Zhanjiang City , Guangdong , China.
b Guangdong Key Laboratory Animal Lab, Guangdong Laboratory Animals Monitoring Institute , Guangzhou , Guangdong , China.
Int J Neurosci. 2019 Apr;129(4):325-336. doi: 10.1080/00207454.2018.1533824. Epub 2018 Nov 2.
The role of n-3 polyunsaturated fatty acid (PUFA) as the main docosahexaenoic acid (DHA) in Alzheimer's disease (AD) remains controversial. Our study aimed to provide detailed information about the role of endogenous n-3 PUFAs in AD.
Here, we generated a fat-1/tau transgenic mouse AD model by crossing female tau mice with male fat-1 mice to exclude confounding variables associated with the benefit of a DHA diet in these AD mice models. PUFAs presented in these AD models were detected by gas chromatography, and the role of endogenous n-3 PUFAs was assessed by lifespan survival assay, behavioral, pathologic, and molecular biology testing as well as imaging of cerebral vasculature.
Endogenous n-3 PUFAs were shown to improve the memory and learning ability of AD mice. One possible reason for this improvement is the reduced formation of neurotrophic factors (NFTs) and Aβ amyloid plaques which usually damage hippocampal neurons. Additionally, endogenous n-3 PUFAs were demonstrated to protect cerebral vascular of AD mice, thereby increasing brain metabolism. Besides, endogenous n-3 PUFAs were observed to extend of the overall survival of tau mouse models.
Endogenous n-3 PUFAs delayed the onset of Alzheimer's disease caused by tau protein dysfunction, alleviating related symptoms and significantly prolonging survival in vivo.
n-3多不饱和脂肪酸(PUFA)作为主要的二十二碳六烯酸(DHA)在阿尔茨海默病(AD)中的作用仍存在争议。我们的研究旨在提供有关内源性n-3多不饱和脂肪酸在AD中作用的详细信息。
在此,我们通过将雌性tau小鼠与雄性fat-1小鼠杂交,构建了fat-1/tau转基因小鼠AD模型,以排除与DHA饮食对这些AD小鼠模型有益作用相关的混杂变量。通过气相色谱法检测这些AD模型中存在的多不饱和脂肪酸,并通过寿命生存试验、行为、病理和分子生物学测试以及脑血管成像来评估内源性n-3多不饱和脂肪酸的作用。
内源性n-3多不饱和脂肪酸被证明可改善AD小鼠的记忆和学习能力。这种改善的一个可能原因是神经营养因子(NFTs)和Aβ淀粉样斑块的形成减少,这些通常会损害海马神经元。此外,内源性n-3多不饱和脂肪酸被证明可保护AD小鼠的脑血管,从而增加脑代谢。此外,观察到内源性n-3多不饱和脂肪酸可延长tau小鼠模型的总体生存期。
内源性n-3多不饱和脂肪酸延迟了由tau蛋白功能障碍引起的阿尔茨海默病的发病,减轻了相关症状,并显著延长了体内生存期。