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毒死蜱诱导大鼠海马神经元突触可塑性失调。

Chlorpyrifos-induced dysregulation of synaptic plasticity in rat hippocampal neurons.

作者信息

Zhou Wenjuan, Zhang Chen, Wang Peipei, Deng Yuanying, Dai Hongmei, Tian Jing, Wu Guojiao, Zhao Lingling

机构信息

Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha, PR China.

出版信息

J Environ Sci Health B. 2023;58(2):100-109. doi: 10.1080/03601234.2023.2171236. Epub 2023 Feb 1.

Abstract

Chlorpyrifos (CPF) is a widely used organophosphorus pesticide. Increasing evidence has shown that exposure to CPF in early life might induce neurodevelopmental disorders, but the pathogenesis remains uncertain. Synaptic plasticity plays a crucial role in neurodevelopment. This study aimed to investigate the effect of CPF on synaptic plasticity in hippocampal neurons and establish the cellular mechanism underlying these effects. Using CPF-exposed rat and primary hippocampal neurons model, we analyzed the impact of CPF on the synaptic morphology, the expression level of a presynaptic protein, a postsynaptic protein and ionotropic glutamate receptors (iGluRs), as well as the effects on the Wnt/β-catenin pathway. We found that the synapses were shortened, the spines were decreased, and the expression of synaptophysin (Syp), postsynaptic density-95 (PSD-95), GluN1, GluA1 and Wnt7a, as well as active β-catenin in primary hippocampal neurons was decreased. Our study suggests that CPF exposure induced dysregulation of synaptic plasticity in rat hippocampal neurons, which might provide novel information regarding the mechanism of CPF-induced neurodevelopmental disorders.

摘要

毒死蜱(CPF)是一种广泛使用的有机磷农药。越来越多的证据表明,生命早期接触CPF可能会诱发神经发育障碍,但其发病机制仍不确定。突触可塑性在神经发育中起着至关重要的作用。本研究旨在探讨CPF对海马神经元突触可塑性的影响,并确定其潜在的细胞机制。利用CPF暴露大鼠和原代海马神经元模型,我们分析了CPF对突触形态、突触前蛋白、突触后蛋白和离子型谷氨酸受体(iGluRs)表达水平的影响,以及对Wnt/β-连环蛋白信号通路的影响。我们发现,原代海马神经元中的突触缩短、树突棘减少,突触素(Syp)、突触后致密蛋白95(PSD-95)、GluN1、GluA1和Wnt7a以及活性β-连环蛋白的表达均降低。我们的研究表明,CPF暴露可导致大鼠海马神经元突触可塑性失调,这可能为CPF诱导神经发育障碍的机制提供新的信息。

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