Fig. 7

Genotype and sex differences in lead-induced reduction of discrimination index over time. The discrimination index in the NOL test was calculated by dividing the difference in exploration time between the novel (c) and familiar (a) locations by the total exploration time, and used to compare changes of spatial memory over time. There was a main effect of lead exposure on the discrimination index in all lead-exposed animals (Multiple mixed-effects linear regression: ApoE3-KI females, p = 0.001; ApoE4-KI females, p < 0.0001; ApoE3-KI males, p = 0.019; ApoE4-KI males, p < 0.0001). a There was no difference in the discrimination index between control and lead-treated ApoE3-KI females during the lead exposure (Two-tailed t-test: 7 week, p = 0.3046; 11 week, p = 0.9977). Lead-treated ApoE3-KI females had a significantly lower discrimination index at 3 and 10 months post-lead exposure (3 months, p = 0.0268; 10 months, p = 0.0156) and a non-significant decrease 6 months post-lead (p = 0.0901) compared to controls. b Lead-treated ApoE4-KI females had a significantly lower discrimination index than ApoE4-KI control mice starting at 7 weeks into the lead exposure and this persisted through 10 months post-lead (7 weeks, p = 0.0016; 11 weeks, p = 0.0002; 3 months, p = 0.0030; 10 months, p = 0.0269). The lead-treated ApoE4-KI discrimination index was lower than controls at 6 months post-lead but not statistically significant (p = 0.0713). c Lead-treated ApoE3-KI males had a significantly lower discrimination index at 6 and 10 months post-lead compared to controls (6 months, p = 0.0356; 10 months, p = 0.0418). d In contrast, lead-treated ApoE4-KI males had a significantly lower discrimination index than controls starting at 11 weeks into the lead exposure and this effect persisted through 10 months post-lead exposure (11 weeks, p = 0.0064; 4 months, p = 0.0433; 6 months, p = 0.0382; 10 months, p = 0.0275). Data are mean ± SEM with n = 8–13 per sex/genotype/treatment. Multi-level mixed-effects linear regression; significant effect of treatment: # p < 0.05; ## p < 0.01; ### p < 0.001. Two-tailed t-test; significant difference between control and lead: n.s., not significant; * p < 0.05; ** p < 0.01; *** p < 0.001