Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice

Abstract

Cadmium (Cd) is a heavy metal of high interest to the superfund initiative. Recent epidemiology studies have suggested a possible association between Cd exposure and cognitive as well as olfactory impairments in humans. However, studies in animal models are needed to establish a direct causal relationship between Cd exposure and impairments in cognition and olfaction. This study aims to investigate the toxic effect of Cd on cognition and olfactory function in mice. One group of 8-week-old C57BL/6 male mice was exposed to 3 mg/l Cd (in the form of CdCl2) through drinking water for 20 weeks for behavior tests and final blood Cd concentration analysis. The behavior tests were conducted before, during, and after Cd exposure to analyze the effects of Cd on cognition and olfactory function. Upon completion of behavior tests, blood was collected to measure final blood Cd concentration. Two additional groups of mice were similarly exposed to Cd for 5 or 13 weeks for peak blood Cd concentration measurement. The peak blood Cd concentration was 2.125-2.25 μg/l whereas the final blood Cd concentration was 0.18 μg/l. At this exposure level, Cd impaired hippocampus-dependent learning and memory in novel object location test, T-maze test, and contextual fear memory test. It also caused deficits in short-term olfactory memory and odor-cued olfactory learning and memory. Results in this study demonstrate a direct relationship between Cd exposure and cognitive as well as olfactory impairments in an animal model.

Caffeine Modulates Cadmium-Induced Oxidative Stress, Neuroinflammation, and Cognitive Impairments by Regulating Nrf-2/HO-1 In Vivo and In Vitro

“…We also found that Cd markedly reduced the expression of synaptic proteins (PSD-95, SNAP-23, and SYN) in the cortex and hippocampus of Cd-treated mice, and administration of caffeine significantly enhanced its expression. Furthermore, studies have reported that Cd is neurotoxic and exposure to Cd is responsible for impaired cognition and memory in several animal models [72,73]. We performed behavioral analysis (MWM and Y-Maze) to measure spatial learning and memory function.…”

Comparative effects of meso-2,3-dimercaptosuccinic acid, monensin, and salinomycin on cadmium-induced brain dysfunction in cadmium-intoxicated mice

“…Cadmium can disturb the homeostasis of Cu and Zn ions in the brain of Cd-intoxicated animals (Wang and Du, 2013 ). It might also induce apoptosis of cerebral cortical neurons by altering Ca homeostasis and the Ca-mediated signalling pathway (Xu et al , 2011 ; Yuan et al , 2013 ).…”

“…A possible mechanism by which Cd induces these disorders may involve alteration of copper (Cu), zinc (Zn), iron (Fe), and calcium (Ca) homeostasis (Wang & Du, 2013 ). Chelation therapy is the most commonly used therapeutic strategy for the treatment of toxic metal poisonings (Flora & Pachauri, 2010 ).…”

Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

“…Studies using animal models suggest that cadmium-induced changes in blood-brain barrier permeability and neuronal damage may be the result of cadmium-mediated generation of reactive oxygen species (ROS) [ [18] , [19] , [20] , [21] , [22] ]. This damage is associated with negative impacts on memory and cognitive behavior [ 23 , 24 ].…”