Co-exposure of metals and high fat diet causes aging like neuropathological changes in non-aged mice brain

Abstract

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.

Keywords: Acetylcholine; Behavior test; Cholinergic system; Hippocampus; Neurodegeneration; Oxidative stress.