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a b
Figure 3: Treatment of amyloid precursor protein (APP) mice with chlorpyrifos oxon CPO results in exacerbated memory deficits. Memory deficits of APP mice
were assessed 2 days after completion of the training in the Morris water maze test by measuring the latency period (a) and distance traveled (b) for animals to
swim to the submerged, invisible platform. The shorter latency periods and shorter distances traveled indicate improved memory. APP mice (control, corn oil alone)
compared to APP mice treated with CPO had shorter mean latency periods. Memory function of wild‑type mice of the same strain and age is shown by the dotted
line, as reported previously. Values are expressed as mean ± standard error of the mean, and n = 12 per group. *Statistically significant (P < 0.05)
[7]

a b
Figure 4: Treatment of amyloid precursor protein (APP) mice with chlorpyrifos oxon (CPO) results in diminished memory retention. The day after the last training
session, the submerged platform was removed and the mice were allowed to swim in the pool for 60 s. The percent time each animal swam in the quadrant from
which the platform had been removed (northeast [NE] quadrant) (a) and the percent time an animal swam in the annulus of the pool were recorded (b). Greater
memory retention is reflected in a higher percent time in the northeast quadrant and lower percent time in the annulus. APP mice (control, corn oil alone) compared
to APP mice treated with CPO had percent times in the quadrant of shorter duration. Values are expressed as the mean ± standard error of the mean, and n = 12
per group. *Statistically significant with P < 0.05
resulted in a 160% and 167% (gestation), 141% and memory deficits that develop in the transgenic APP
152% (lactation) and 140% and 142% (weanling) mice.
increase in the latency period and distance traveled,
respectively [Figure 3a and b]. The 16 s latency Administration of chlorpyrifos oxon to amyloid precursor
period, and the 72 cm distance are the time and protein mice exacerbates brain amyloid plaque load
distance for wild-type mice (nontransgenic, same Aβ immunohistochemistry of brain sections showed
strain as APP mice) [Figure 3a and b, dotted lines]. that the treatment with CPO increased brain
amyloid plaques in the APP mice [Figure 5a and b].
Administration of CPO resulted in substantial memory Administration of CPO under all paradigms resulted
loss in the APP mice as illustrated by the reduced in an increase in amyloid plaque load in the APP
percent time spent in the NE quadrant (from which the mice [Figure 5c]. Quantitative image analysis of the Aβ
submerged platform was removed), and the increased immunohistochemistry showed that the CPO resulted
percent time spent in the outer annulus, compared in a significant 214% (gestation), 234% (lactation) and
to control APP mice [Figure 4]. The CPO treatment 215% (weanling) increase in brain amyloid plaque
resulted in a 48% (gestation), 46% (lactation) load relative to control APP animals [Figure 5c].
and 35% (weanling) decrease in the percent time
spent in the NE quadrant and a 215% (gestation), Administration of chlorpyrifos oxon alters brain biomarkers
213% (lactation) and 233% (weanling) increase in a manner characteristic of inflammation and increase in
in the percent time spent in the annulus. The APP amyloid precursor protein processing by β-secretase
mice (control) and APP CPO mice did not have a Amyloid precursor protein-derived Aβ peptides
different swimming speed (data not shown). Thus, and APP-derived cleavage products resulting from
by the four parameters measured in the Morris water amyloidogenic and nonamyloidogenic processing of
maze test, the CPO administration exacerbated the APP were evaluated in the control and CPO treated

Neuroimmunol Neuroinflammation | Volume 2 | Issue 1 | January 15, 2015 35