Hu Qiansheng, Fu Hongjun, Ren Tieling, Wang Shuyu, Zhou Wei, Song Hong, Han Yifan, Dong Shengzhang
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, China.
Neurotoxicology. 2008 Jul;29(4):675-81. doi: 10.1016/j.neuro.2008.04.002. Epub 2008 May 21.
Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for cell migration and neurite outgrowth. Developmental lead (Pb) exposure has been considered to affect the expression of PSA-NCAM, which contributes to the neurotoxicity of Pb exposure. However, the effect of maternal low-level Pb exposure on the expression of PSA-NCAM in neonatal rat pups has not been reported. In the present study, female Wistar rats were exposed to vehicle or different dosages of lead chloride (0.5-4mM PbCl2) 2 weeks before and during pregnancy. This exposure protocol resulted in neonatal rat pups blood Pb levels up to 12.12+/-0.38 microg/dl, and hippocampal Pb levels up to 9.22+/-0.81 microg/g at postnatal day 1 (PND 1). Immunohistochemistry analysis and Western blot analysis revealed that the expressions of PSA-NCAM and NCAM in the hippocampi of neonatal rat pups at PND 1 were significantly reduced by the maternal low-level Pb exposures. Furthermore, the mRNA levels of NCAM and polysialyltransferases (STX and PST), measured by the fluorescent real-time quantitative RT-PCR, dosage-dependently and significantly decreased by 13.26-37.62%, 25.17-59.67%, and 10.78-47.81%, respectively. In addition, the sialyltransferase activity in neonatal rat pups was significantly reduced by 6.23-32.50% in the presence of the low-level Pb exposure, too. Taken together, these results suggest that maternal low-level Pb exposure reduces the expression of PSA-NCAM, NCAM, and the activity of sialyltransferase in the hippocampi of neonatal rat pups, which might contribute to the learning and memory impairments in the developmental pups following maternal low-level Pb exposure.
高度多聚唾液酸化神经细胞黏附分子（PSA-NCAM）在新生成的细胞中短暂特异性表达，对细胞迁移和神经突生长很重要。发育期铅（Pb）暴露被认为会影响PSA-NCAM的表达，这与铅暴露的神经毒性有关。然而，母体低水平铅暴露对新生大鼠幼崽中PSA-NCAM表达的影响尚未见报道。在本研究中，雌性Wistar大鼠在怀孕前2周及怀孕期间暴露于赋形剂或不同剂量的氯化铅（0.5 - 4 mM PbCl2）。这种暴露方案导致新生大鼠幼崽在出生后第1天（PND 1）的血铅水平高达12.12±0.38 μg/dl，海马铅水平高达9.22±0.81 μg/g。免疫组织化学分析和蛋白质印迹分析显示，母体低水平铅暴露显著降低了PND 1新生大鼠幼崽海马中PSA-NCAM和NCAM的表达。此外，通过荧光实时定量RT-PCR测量的NCAM和多聚唾液酸转移酶（STX和PST）的mRNA水平分别剂量依赖性且显著降低了13.26 - 37.62%、25.17 - 59.67%和10.78 - 47.81%。另外，在低水平铅暴露情况下，新生大鼠幼崽中的唾液酸转移酶活性也显著降低了6.23 - 32.50%。综上所述，这些结果表明母体低水平铅暴露会降低新生大鼠幼崽海马中PSA-NCAM、NCAM的表达以及唾液酸转移酶的活性，这可能导致母体低水平铅暴露后发育中的幼崽出现学习和记忆障碍。
