Differential expression of SLC30A10 and RAGE in mouse pups by early life lead exposure

Background: SLC30A10 and RAGE are widely recognized as pivotal regulators of Aβ plaque transport and accumulation. Prior investigations have established a link between early lead exposure and cerebral harm in offspring, attributable to Aβ buildup and amyloid plaque deposition. However, the impact of lead on the protein expression of SLC30A10 and RAGE has yet to be elucidated. This study seeks to confirm the influence of maternal lead exposure during pregnancy, specifically through lead-containing drinking water, on the protein expression of SLC30A10 and RAGE in mice offspring. Furthermore, this research aims to provide further evidence of lead-induced neurotoxicity.

Methods: Four cohorts of mice were subjected to lead exposure at concentrations of 0 mM, 0.25 mM, 0.5 mM, and 1 mM over a period of 42 uninterrupted days, spanning from pregnancy to the weaning phase. On postnatal day 21, the offspring mice underwent assessments. The levels of lead in the blood, hippocampus, and cerebral cortex were scrutinized, while the mice's cognitive abilities pertaining to learning and memory were probed through the utilization of the Morris water maze. Furthermore, Western blotting and immunofluorescence techniques were employed to analyze the expression levels of SLC30A10 and RAGE in the hippocampus and cerebral cortex.

Results: The findings revealed a significant elevation in lead concentration within the brains and bloodstreams of mice, mirroring the increased lead exposure experienced by their mothers during the designated period (P < 0.05). Notably, in the Morris water maze assessment, the lead-exposed group exhibited noticeably diminished spatial memory compared to the control group (P < 0.05). Both immunofluorescence and Western blot analyses effectively demonstrated the concomitant impact of varying lead exposure levels on the hippocampal and cerebral cortex regions of the offspring. The expression levels of SLC30A10 displayed a negative correlation with lead doses (P < 0.05). Surprisingly, under identical circumstances, the expression of RAGE in the hippocampus and cortex of the offspring exhibited a positive correlation with lead doses (P < 0.05).

Conclusion: SLC30A10 potentially exerts distinct influence on exacerbated Aβ accumulation and transportation in contrast to RAGE. Disparities in brain expression of RAGE and SLC30A10 may contribute to the neurotoxic effects induced by lead.