Calcium carbonate supplementation causes memory impairment in mice

ABSTRACT

Objective:To investigate the influence of calcium carbonate supplementation on cognitive function in mice.Methods:Mice were fed diets containing 1.0% calcium carbonate for 8 weeks, following which they were evaluated for memory function using object recognition, Y-maze, and Barnes maze tests. Next, the expression levels of cAMP response element binding protein (CREB) and phosphorylated CREB, which is involved in the memory process were investigated in both the hippocampus and cerebral cortex using western blotting methods.Results:Mice fed on a diet containing calcium carbonate showed memory impairments in object recognition, Y-maze, and Barnes maze tests with respect to the mice that were on a control diet. Further, mice that were fed a diet containing calcium carbonate and a nimodipine (an L-type calcium channel antagonist), reversed calcium carbonate-induced memory impairments, thus suggesting that excessive entry of calcium in cells may cause memory impairments. A study using western blot revealed that expression of CREB and phosphorylated CREB in hippocampus and cerebral cortex was significantly lower in the calcium carbonate-fed mice than in the control-diet-fed mice.Conclusions:These results suggest that a calcium carbonate diet may cause memory impairment by decreasing CREB expression. This is the first report of calcium carbonate supplementation causing memory impairment. This simple animal model may be useful as a novel cognitive impairment model for drug development.