Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.
Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.
Brain Res Bull. 2019 Apr;147:148-158. doi: 10.1016/j.brainresbull.2019.02.013. Epub 2019 Feb 23.
In recent decades, humans' exposure to metals have increased due to industrialization and socioeconomic trends have caused increased high fat diet (HFD) consumption. Concurrently, metals and HFD are risk factors for health, and in particular, the cognitive impairment. The aim of this study was to evaluate the effect of metals and HFD treatment on neuropathological changes in young mice brain, and compare with untreated young mice (8-11 weeks = 2-3 months) and aged mice (12 months). Mice were given 300 ppm of Aluminum (Al), Copper (Cu), Lead (Pb) and Cadmium (Cd) in drinking water and HFD feed (40% of the feed weight was animal fat) for 42 days. Metals+HFD treated mice were subjected to behavior tests, such as, Morris water maze, elevated plus maze, fear condition and contextual memory to evaluate memory levels. Spatial memory (p < 0.01), contextual memory (p < 0.01) and fear memory (p < 0.05) were significantly impaired in metals+HFD group compared to young mice. The extent of neurodegeneration with metals+HFD co-exposure was considerably high in hippocampus (p < 0.01) and cortex (p < 0.01), compared to aged mice brain and untreated young mice. Increased oxidative stress was recorded in the cortex, hippocampus and amygdala of metals+HFD group compared to the young (p < 0.001) and aged group (p < 0.05). The acetylcholine concentration decreased in cortex, hippocampus and amygdala of metals+HFD group, explaining the cholinergic deficits that caused cognitive impairment. Among the studied metals, Al was found to be highly accumulated in cortex (p < 0.01), hippocampus (p < 0.01) and amygdala (p < 0.01); followed by Pb, Cu and Cd. Hippocampus showed greater accumulation of metals than the cortex and amygdala. This data provided the novel evidences that combined administration of metals and HFD enhanced aging process, caused memory impairment, cholinergic hypofunction, elevated oxidative stress and neurodegeneration in young mice.
近几十年来，由于工业化和社会经济趋势的发展，人类接触金属的程度有所增加，导致高脂肪饮食（HFD）的消费增加。同时，金属和 HFD 是健康的危险因素，特别是认知障碍。本研究旨在评估金属和 HFD 处理对年轻小鼠大脑神经病理学变化的影响，并与未经处理的年轻小鼠（8-11 周龄=2-3 个月）和老年小鼠（12 个月）进行比较。小鼠饮用含 300ppm 铝（Al）、铜（Cu）、铅（Pb）和镉（Cd）的水和 HFD 饲料（饲料重量的 40%为动物脂肪）42 天。金属+HFD 处理的小鼠接受行为测试，如 Morris 水迷宫、高架十字迷宫、恐惧条件和情景记忆，以评估记忆水平。与年轻小鼠相比，金属+HFD 组的空间记忆（p<0.01）、情景记忆（p<0.01）和恐惧记忆（p<0.05）显著受损。与老年小鼠和未经处理的年轻小鼠相比，金属+HFD 共暴露后海马体（p<0.01）和皮质（p<0.01）的神经退行性变程度相当高。与年轻（p<0.001）和老年（p<0.05）组相比，金属+HFD 组的皮质、海马体和杏仁核的氧化应激增加。金属+HFD 组的皮质、海马体和杏仁核中的乙酰胆碱浓度降低，解释了导致认知障碍的胆碱能缺陷。在所研究的金属中，Al 被发现高度积累在皮质（p<0.01）、海马体（p<0.01）和杏仁核（p<0.01）；其次是 Pb、Cu 和 Cd。海马体的金属积累量大于皮质和杏仁核。这些数据提供了新的证据，即金属和 HFD 的联合给药增强了年轻小鼠的衰老过程，导致记忆障碍、胆碱能功能低下、氧化应激升高和神经退行性变。
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