Abstract:

Objective To explore the mechanism of Lactobacillus plantarum (L. plantarum) for alleviating learning and memory impairments caused by lead exposure. Methods Twenty-four C57BL/6J mice were randomized equally into control group, lead exposure (100 mg/L) group, and L.plantarum treatment group with daily gavage of L.plantarum (10⁹ CFU) for 10 weeks. Learning and memory abilities of the mice were evaluated using Morris water maze test, and blood lead level and bile acid levels were determined using inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography-mass spectrometry (LC-MS), respectively. Hippocampal pathologies of the mice were examined with HE staining, and immunohistochemistry was used to observe morphological changes and microglia activation in the hippocampus. Serum levels of TNF‑α and IL-1β of the mice were determined with ELISA, and hippocampal expression levels of NLRP3 and TGR5 proteins were detected using Western blotting. Results Compared with those in lead exposure group, the mice receiving L.plantarum intervention showed significantly increased exploration time, swimming distance, and target platform crossings with reduced latency period to find the hidden platforms in Morris water maze test. L.plantarum intervention partially reversed lead exposure induced reduction of serum levels of deoxycholic acid, 3-hydroxydeoxycholic acid, 3-hydroxyursodeoxycholic acid, 3-thiodeoxycholic acid, and 3-thio‑α‑methylcholic acid. The treatment also significantly reduced hippocampus pathologies in mice with lead exposure, and reduced their serum levels of IL-1β and TNF‑α and hippocampal NLRP3 protein expression levels. Conclusion L.plantarum can alleviate learning and memory impairments caused by lead exposure in mice possibly by regulating bile acid metabolism and inhibiting hippocampal expression of NLRP3 protein.

Key words: lead exposure, learning and memory, Lactobacillus plantarum, targeted metabolomics, NLRP3