不同ω-3多不饱和脂肪酸对斑马鱼阿尔茨海默病模型记忆损伤和神经病理学变化影响Effects of Different ω-3 Polyunsaturated Fatty Acids on Memory Impairment and Neuropathological Changes in Zebrafish Alzheimer's Disease Model
钟绮媚,张晶晶,杨志友,邓淑怡,王佳佳,张才,张永平,宋采
摘要(Abstract):
【目的】研究ω-3多不饱和脂肪酸(PUFAs)二十碳五烯酸(EPA)、二十二碳五烯酸(DPA)和二十二碳六烯酸(DHA)对铝致斑马鱼认知、记忆损伤和病理变化的影响。【方法】利用共聚焦显微镜观察斑马鱼幼鱼脑内荧光强度。以100μg/L铝诱导斑马鱼阿尔茨海默病(AD)模型,给予EPA、DPA和DHA后,进行新物体识别和T迷宫奖赏测试,Elisa检测β-Amyloid(Aβ)、p-tau、乙酰胆碱酯酶(AChE)和白细胞介素(IL)-1β的含量,qPCR检测小胶质细胞标志物Hexb与星形胶质细胞标志物GFAP及脑源性神经营养因子(BDNF)的变化。【结果】与对照组相比,铝显著激活斑马鱼幼鱼脑内的小胶质细胞。在行为实验中,与对照组相比,铝显著延长到达新臂、奖励臂潜伏期,减少在新臂、奖励臂时间;EPA、DPA和DHA均显著增加在新臂、奖励臂时间;EPA和DHA显著减少到达奖励臂的潜伏期;与对照组相比,模型组显著增加Aβ、p-tau、AChE和IL-1β的蛋白浓度以及Hexb和GFAP的mRNA表达。EPA、DPA和DHA均显著降低Aβ蛋白浓度和GFAP的mRNA表达。EPA显著降低p-tau、AChE和IL-1β的蛋白浓度,并抑制Hexb及上调BDNF的mRNA表达;DPA亦显著降低p-tau蛋白浓度;DHA显著降低AChE浓度。【结论】三种ω-3PUFAs对斑马鱼AD样变化作用各不相同,EPA的效果最佳。
关键词(KeyWords): 3多不饱和脂肪酸;阿尔茨海默病;神经炎症;斑马鱼;学习记忆
基金项目(Foundation): 广东省自然科学基金(2021A1515011579);; 深圳市科技计划(国际合作研究)项目(GJHZ20190823111414825);; 广东省科技计划项目(2016B020235001)
作者(Author): 钟绮媚,张晶晶,杨志友,邓淑怡,王佳佳,张才,张永平,宋采
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