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

Abstract It is well known that SLC30A10 and RAGE play a crucial role in regulating the transport and accumulation of Aβ plaques. Our previous studies have shown that early exposure to lead can cause cerebral damage to pups due to the accumulation of Aβ and the deposition of amyloid plaques. However, the effect of lead on the protein expression levels of SLC30A10 and RAGE remains unclear. This study aimed to verify that maternal exposure to lead-containing drinking water during pregnancy would affect the expression of SLC30A10 and RAGE proteins in mice offspring, further verifying the lead-induced neurotoxicity. Four groups of mice were exposed to 0 mM, 0.25 mM, 0.5 mM, and 1 mM of lead for 42 consecutive days from pregnancy to weaning, and the offspring mice were tested on postnatal day 21. The levels of lead in the blood, hippocampus, and cerebral cortex were examined; the learning and memory abilities of the mice were investigated using the Morris water maze; the expression levels of SLC30A10 and RAGE in the hippocampus and cerebral cortex were examined using Western blotting and immunofluorescence. The results showed that the lead concentration in the brain and blood of the mice increased along with the lead content of the mothers during the lead exposure period (P < 0.05). In the Morris water maze test, the spatial memory of the lead exposure group was lower than that of the control group (P < 0.05). Both Immunofluorescence and Western blot analysis showed that the hippocampal and cerebral cortex of the offspring were proportionally affected by differential levels of lead exposure. The expression levels of SLC30A10 were negatively correlated with lead doses (P < 0.05). Surprisingly, under the same conditions, the expression of RAGE in the hippocampus and cortex of offspring was positively correlated with lead doses (P < 0.05). SLC30A10 may play a differential role in aggravated Aβ accumulation and transportation compared with RAGE. A difference in RAGE and SLC30A10 expression in the brain could contribute to lead-induced neurotoxicity.