Abstract:
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.
