Effects of Prenatal Dietary Enhancement of Iron on βeta Amyloid (Aβ) Plaques and Behavior in Tg2576 and Wt2576 Mice




Thompson, James H.

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This thesis investigated the relationship of iron in the brain enhanced by an elevated level in the drinking water and Amyloid precursor protein (APP) in a transgenic (Tg) model of Alzheimer’s disease. Mice were given water containing 10ppm FeNO3 and lab tap water prenatally and from birth. After reaching one year of age animals were tested in a Morris water maze (MWM), a behavioral test of spatial learning and memory and assessed for behavioral deficits associated with Alzheimer’s pathology and enhanced supplementation of iron. After completion of behavioral testing, mice were sacrificed and brains were harvested for histological examination to explore plaque formation. This was done using a Congo red stain and Image J software, which quantifies plaque load and plaque type using electron microscopy and a polarizing lens. Research showed that supplementation of Fe in the drinking water had an impact on both plaque area (Tg mice only) and behavior in both groups of Fe treated mice. For MWM probe trial percent in quadrant Fe Tg mice spent more time in the correct quadrant than lab Tg, p < .05. Lab Wt mice spent more time in the correct quadrant than lab Tg, p< .01. For the moving platform, on day 1 Wt mice had faster escape latencies than Tg mice, p< .01, and on day 2 Wt mice also had faster escape latencies than Tg, p< .01. In addition, Fe mice had faster escape latencies than lab water treated mice, p< .05. Thus, overall these results indicate that Fe treated groups and Wt lab mice performed better in the MWM than the lab Tg group. Histological analysis revealed that lab Tg mice had more plaques than Fe Tg mice, p< .01. There was also a main effect of plaque type with more normal plaques than birefringent plaques, p< .01. This suggests that reduced plaque burden leads to a reduced impairment in the MWM. Recent information has pointed to a recessive blindness gene in the Tg2576 mouse model of AD. Swim patterns have been examined, and it is thought that some Wt mice with slow latencies may have been blind. As a result, current results are being further examined, and tails will be genotyped if possible. This is being done to determine if the data presented in this thesis are as accurate as possible. Preliminary analyses are reported here, but results may change once it is determined which if any animals were blind.



Alzheimer’s, Behavior, Iron, Amyloid, Tg2576