Effects of ZnCON3 Supplementation in a Transgenic Model of Alzheimer’s Disease
Mentor: Paul Adlard, Carl Cotman & J. Patrick Kesslak
Previous studies have suggested that low levels of zinc in the brain may contribute to impairments in nervous, endocrine and immune systems, and this may be related to deficiencies in antioxidant defense mechanisms. Furthermore, aged mice show impairments in cognition, one of the characteristics of Alzheimer's disease (AD) that correlate with decreased levels of zinc. The reasoning is that high levels of oxidative stress (due to low antioxidants), may make aged brains susceptible to free radical mechanisms. While many studies have examined the effects of low zinc levels on the brain, we are exploring the effect of high concentrations of zinc in the brain. Since the mechanism of zinc mimic that of endogeneous calcium, we predict high levels of zinc will also a have neurotoxic effect. We gave ZnCO3 in drinking water supplementation to double mutated transgenic mice (TgCRND8), an animal model for Alzheimer’s disease, four months following weaning. Then, mice underwent Morris Water Maze testing in conjunction with the Atlantis Platform to test reference memory, followed by the moving platform task to test for short-term memory. The final day tested for blindness. After sacrificing mice, immunohistochemisty fluorescence was performed to determine amyloid plaque densities. Preliminary results show high frequency in platform finds for control groups compared to the experimental group which suggests that the elevated zinc levels have had a negative effect on the brain. However, immunohistochemistry revealed no difference in plaque density among zn+/tg and zinc-/tg groups.