Perinatal Lead Exposure Alters Calsyntenin-2 and Calsyntenin-3 Expression in the Hippocampus and Causes Learning Deficits in Mice Post-weaning.

Ning Li, Shuai Cao, Zengli Yu, Mingwu Qiao, Yongxia Cheng, Yue Shen, Lianjun Song, Xianqing Huang, Guojun Yang, Yali Zhao

Biological trace element research 2021 Apr

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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.

Citation

Ning Li, Shuai Cao, Zengli Yu, Mingwu Qiao, Yongxia Cheng, Yue Shen, Lianjun Song, Xianqing Huang, Guojun Yang, Yali Zhao. Perinatal Lead Exposure Alters Calsyntenin-2 and Calsyntenin-3 Expression in the Hippocampus and Causes Learning Deficits in Mice Post-weaning. Biological trace element research. 2021 Apr;199(4):1414-1424