背景:SLC30A10和RAGE被广泛认为是Aβ斑块转运和积累的关键调节剂。先前的调查已经建立了早期铅暴露与后代大脑伤害之间的联系,可归因于Aβ积聚和淀粉样斑块沉积。然而,铅对SLC30A10和RAGE蛋白表达的影响尚待阐明。这项研究旨在确认孕妇在怀孕期间铅暴露的影响,特别是通过含铅的饮用水,SLC30A10和RAGE在子代小鼠中的蛋白表达。此外,本研究旨在为铅引起的神经毒性提供进一步的证据.
方法:对四组小鼠进行0mM浓度的铅暴露,0.25mM,0.5mM,在42天不间断的时间内达到1mM,从怀孕到断奶阶段。在出生后第21天,对后代小鼠进行评估。血液中的铅含量,海马体,大脑皮层被仔细检查,而小鼠的认知能力有关的学习和记忆是通过利用莫里斯水迷宫。此外,采用蛋白质印迹和免疫荧光技术分析SLC30A10和RAGE在海马和大脑皮层中的表达水平。
结果:研究结果表明,小鼠大脑和血液中的铅浓度显著升高,反映了母亲在指定期间经历的铅暴露增加(P<0.05)。值得注意的是,在莫里斯水迷宫评估中,与对照组相比,铅暴露组的空间记忆显着降低(P<0.05)。免疫荧光和Western印迹分析均有效地证明了不同的铅暴露水平对后代海马和大脑皮层区域的伴随影响。SLC30A10的表达水平与铅剂量呈负相关(P<0.05)。令人惊讶的是,在相同的情况下,子代海马和皮质中RAGE的表达与铅剂量呈正相关(P<0.05)。
结论:与RAGE相比,SLC30A10可能对加剧的Aβ积累和转运产生不同的影响。RAGE和SLC30A10的脑表达差异可能是铅引起的神经毒性作用的原因。
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).
CONCLUSIONS: 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.