To investigate the effect of subchronic benzo[a]pyrene (BaP) toxicity on tau protein phosphorylation and mild cognitive dysfunction in HAPOE4 mice.

24 male C57BL/6 wild-type and HAPOE4 mice were used in this study, 12 of each type. The mice were randomly divided into three groups: vehicle group (olive oil), low-dose BaP-treated group (2.5 mg/kg), and high-dose BaP-treated group (6.25 mg/kg), with 8 mice in each group. The mice were injected with BaP via the peritoneal cavity and weighed before and after injection. The exposure period was 90 days. The Morris water maze test was used to detect the mice’s learning and memory abilities, the tail suspension test was used to detect the mice’s depressive state, the silver glycinate dip staining was used to observe the neurofibrillary tangles in mouse brain tissue sections, and immunohistochemistry was used to detect the protein expression of APOE, LRP1, tau, p-tau (Ser199), and p-tau (Ser396) in the hippocampus of the mice. ANOVA was used for the comparison of the above count data, the two-sample t-test was used for the comparison between genotypes, and the factorial analysis method was used to verify the interaction between the treatment and genotype.

The results of the water maze behavior experiment: the results of the positioning navigation experiment: the escape latency length of each group decreased with the increase of training days, and the escape latency of HAPOE4 mice with the same dose of poison was higher than that of WT type. There were differences in escape latency between groups on the 4th and 5th days. Both genotype and toxicity could lead to a decrease in the number of crossings of the platform and the residence time in the target quadrant, but there was no significant interaction between genotype and toxicity. The results of tail suspension experiment: genotype and poisoning had an interactive effect on the immobility time of mice, and both of them would lead to an increase in the immobility time of mice. The results of silver glycinate dipping experiment: both genotype and poisoning would cause the dyeing to deepen and increase in mice. The results of immunohistochemistry showed that genotype and poisoning had an interactive effect on the MOD values of APOE, LRP1, tau, p-tau (ser199) and p-tau (ser396), and all of them led to an increase in MOD values.

BaP and APOE4 genes affected spatial learning and memory ability and depression in mice, and BaP and APOE4 genes interacted with the immobility time of tail suspension experiments, indicating that the combined effect of BaP and APOE4 genes may have an effect on the depressed state of mice; and BaP and APOE4 genes interacted with abnormal phosphorylation of tau protein in mice, indicating that subchronicBaP infection could lead to tau protein phosphorylation and mild cognitive dysfunction in mice with HAPOE4 genotype, which may be caused by the combined effect of BaP and APOE4 genes resulting in the increase of APOE and LRP1 in mice.