Fig. 4

Lead impairs contextual fear memory in lead-treated ApoE4-KI females at 22–24 weeks of age. a Schematic of cued and contextual fear conditioning test performed post-lead exposure. b, c Female and male mice had low baseline freezing behavior (Pre-shock). In the 24 h Context test, there was a significant main effect of lead treatment on freezing behavior in both males and females (Two-way ANOVA: females, F_(1,33) = 6.803, p =0.0136; males, F_(1,42) = 4.435, p =0.0412). Although lead treatment reduced contextual memory in all animals (manifested as reduced freezing 24 h after fear conditioning) post-hoc tests revealed that this was only statistically significant between control and lead-treated ApoE4-KI females (Holm-Sidak post-hoc test: F_(1,33) = 2.648, p = 0.0245). Auditory-cued (hippocampus-independent) fear memory was not affected (Cued test) in any lead-exposed animals. All animals did not freeze when placed into a novel, non-shock context (Novel context test). Data are mean ± SEM with n = 8–13 per sex/genotype/treatment. Two-way ANOVA with Holm-Sidak post-hoc test. n.s. not significant; * p < 0.05