Effect of long-term lead exposure on amyloid precursor protein and tau gene expressions in rat hippocampus

Objective To investigate changes in amyloid precursor protein (APP) and tau gene expression in hippocampus of rat with long-term lead exposure.Methods Female and male (at the ratio of 2:1) specific-pathogen free Sprague-Dawley rats were randomly divided into three groups:control group supplied with distilled water,low lead exposure group (LLG) with drinking water containing lead acetate of 800 mg/L,and high lead exposure group (HLG) with drinking water containing lead acetate of 1 000 mg/L.Then the male offsprings were continuously exposed to drinking water containing lead acetate of 0 mg/L (control group),300 mg/L (LLG),and 900 mg/L (HLG)mg/L and lead content in blood and hippocampus tissue of the offsprings were measured at postnatal week 3 (PNW3),postnatal week 41 (PNW41) and postnatal week 70 (PNW70);the mRNA and protein expressions of tau and APP in hippocampus of the offsprings were determined simultaneously with real-time quantitative PCR(qPCR)and Western blot.Results Compared with those of the control group,the lead content of blood and hippocampus were significantly increased in lead-exposed male offsprings (P < 0.05).The expression of APP mRNA(1.398±0.827) and protein (1.454±0.190) were significantly up-regulated in PNW70 male hippocampus of offsprings in HLG (P < 0.05).Compared with those of the control group,the expression of tau protein of the offsprings in LLG (4.850±1.257) and HLG (5.557±1.880)were significantly increased at PNW3 (P < 0.01),and the expression of phosphorylated tau protein (3.225±1.098) increased in male offspring's hippocampus of HLG at PNW70 (P < 0.05).Conclusion Long-term lead exposure induces up-regulations of mRNA and protein of APP and tau in hippocampus of rats at PNW3 and PNW70.