Neurobehavioral and neurophysiological effects produced by enhanced consumption of zinc, zinc plus copper, and iron in APP2576 mice as assessed through novel object recognition and histopathology




Groeber, Caitlin M.

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This study examined the effect of drinking water enhancement with specific metal ions, which are commonly found in the brain, and the impact on an animal model of Alzheimer’s disease (AD). Mice with the amyloid precursor protein (APP) Tg2576 mutation were used to examine the effect of metal iron overload on brain pathology and behavioral outcomes. Transgenic (Tg) and wild-type (wt) mice were placed into one of the following water groups zinc-enhanced water (10ppm ZnCO3), zinc plus copper-enhanced water (10ppm ZnCO3, 2ppm Cu), iron enhanced water (10ppm FeNO3), or lab tap water. Two groups were tested, group 1 examined initial prenatal exposure to iron and group 2 examined initial exposure to all metals at adolescence (or three months of age). At twelve months animals were tested in the novel object recognition (NOR) apparatus, a behavioral assessment of recognition memory. After testing, animals were sacrificed and histological brain analyses were conducted on transgenic animals to determine differential changes in plaque pathology by Congo red staining. The results of this study showed that the NOR task has the potential to be used as a standard recognition (memory) deficit task for transgenic mice. Transgenic animals consistently sniffed for a shorter duration on the novel object than the wild-type animals, in both the prenatal and adolescent exposure groups. There was no significant difference for any water types, indicating metal enhancement may affect novel object recognition. However, unexpectedly, the results showed that animals raised on iron-enhanced water performed better than lab tap water animals. In group 1, Tg lab animals failed to show object recognition while Tg iron animals maintained object recognition. In group 2, iron animals sniffed more than lab animals on either the standard or the novel object, regardless of genotype. Also unexpectedly, there was no change in object recognition due to either initial prenatal or adolescent exposure to iron. Although increased exposure to iron did not impair novel object recognition, it did diminish the level of sniffing. This suggests that regardless of the exposure time to iron-enhanced water, there is evidence to suggest a remediation effect of recognition memory for these mice due to iron enhancement. For both groups, plaque load was dependent on region of interest with higher plaque burden in the hippocampus. This was expected as the hippocampus is one of the first areas of the brain to develop plaques in AD. Overall, these results indicate that NOR can be used to assess transgenic mice and that iron may exhibit a rescuing effect for recognition memory deficits caused by the Alzheimer’s disease.



Alzheimer’s disease, Zinc, Iron, Object recognition, Copper, Plaque