Calsyntenin-2 (Clstn2) and calsyntenin-3 (Clstn3) are the members of the cadherin superfamily and function to regulate the postsynaptic activity. Both proteins are known to play an important role in memory and learning. This study was designed to test the hypothesis that exposure of mothers to Pb in drinking water may alter the expression of Clstn2 and Clstn3 in offspring, which contributes to the Pb-induced learning deficiency. Pregnant mice were exposed to Pb in drinking water as Pb acetate from gestation to weaning. At the postnatal day 21, the learning and memory ability of pups was tested by Morris water maze, and the blood and brain tissues from pups were collected for metal and protein analyses. Data showed that perinatal Pb exposure resulted in a dose-dependent increase of Pb concentrations in blood (6–20-fold), hippocampus (2–7-fold), and cerebral cortex (2–8-fold) in offspring, as compared to controls (p < 0.05).The ability of learning and memory was decreased in lead exposure group, as compared to controls (p < 0.05). Both immunofluorescence and Western blot analyses revealed a striking difference in the expression of Clstn2 vs. Clstn3 following perinatal Pb exposure. In pregnant mice exposed to 0.1%, 0.2%, and 0.5% Pb, the expression of Clstn2 in offspring showed a Pb dose-related decrease by 39.2%, 76.5%, and 96.1% in hippocampus and by12.5%, 59.4%, and 78.1% in cerebral cortex, respectively (p < 0.05). In contrast, Clstn3 expression in these offspring brain regions was significantly increased (p < 0.05), after perinatal Pb exposure. The nature of Pb differential effect on Clstn2 and Clstn3 remains unknown. These observations suggest that Clstn2 and Clstn3 may have different roles in synaptic development and differentiation. Pb-induced learning defects may partly relate to the altered expression of calsyntenin proteins.

Calsyntenin-2（Clstn2）和Calsyntenin-3（Clstn3）是钙粘蛋白超家族的成员，并具有调节突触后活性的功能。已知这两种蛋白在记忆和学习中起重要作用。这项研究旨在检验以下假设：母亲在饮用水中接触Pb可能会改变后代中Clstn2和Clstn3的表达，从而加剧了Pb引起的学习障碍。从怀孕到断奶，怀孕的小鼠都在饮用水中暴露于Pb乙酸盐。在出生后第21天，用莫里斯水迷宫测试幼犬的学习和记忆能力，并收集幼犬的血液和脑组织进行金属和蛋白质分析。数据显示，围产期Pb暴露导致血液，海马（2-7倍）中Pb浓度呈剂量依赖性增加，p  <0.05）。铅暴露组的学习和记忆能力与对照组相比有所下降（p  <0.05）。免疫荧光和蛋白质印迹分析均显示，围产期铅暴露后，Clstn2与Clstn3的表达存在显着差异。在暴露于0.1％，0.2％和0.5％Pb的怀孕小鼠中，后代Clstn2的表达与剂量相关，在海马中分别下降了39.2％，76.5％和96.1％，在海马中下降了12.5％，59.4％，和78.1％分别位于大脑皮层（p <0.05）。相反，围产期铅暴露后，这些子代大脑区域的Clstn3表达显着增加（p <0.05）。铅对Clstn2和Clstn3的微分作用的性质仍然未知。这些观察结果表明Clstn2和Clstn3在突触发展和分化中可能具有不同的作用。铅诱导的学习缺陷可能部分与钙调蛋白的表达改变有关。