Effects of chronic lead acetate exposure on neurobehavior and serum metabolomics in mice

[Background] Chronic low-level exposure to lead can damage the central nervous system and cause anxiety-like behavior. However, whether changes of blood metabolites occur in this process and its relationship with lead-induced neurobehavioral disorder remain unclear. [Objective] To explore the effects of chronic lead acetate (PbAc) exposure at different concentrations on anxiety-like behavior and serum metabolites and their relationships in mice, as well as the mechanism of lead exposure on neurobehavioral injury in mice from the perspective of metabolomics. [Methods] A total of 64 healthy 4-week-old C57BL/6J mice, half male and half female, were randomly divided into four groups: control group (normal drinking water), 20 mg·L−1 PbAc group, 100 mg·L−1 PbAc group, and 500 mg·L−1 PbAc group. After 10 weeks of free drinking of water containing designed concentrations of PbAc, the mice were tested for anxiety-like behavioral changes by open field experiment. After the mice were anesthetized, blood was collected from the eyes, the serum was separated, and the effects of designed doses of lead exposure on metabolites in the serum of mice were compared by liquid chromatography with tandem mass spectrometry combined with principal component analysis and partial least squares discrimination analysis. [Results] The results of the open field experiment showed that the reductions in movement time spent in central area in the 100 mg·L−1 and 500 mg·L−1 PbAc groups compared with the control group were of statistical significance (P