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多氯联苯破坏海马神经元中的肌动蛋白细胞骨架。

Polychlorinated biphenyls disrupt the actin cytoskeleton in hippocampal neurons.

机构信息

Department of Children's Environmental Health, XinHua Hospital, Shanghai JiaoTong University, Shanghai 200092, China.

出版信息

Environ Toxicol Pharmacol. 2007 Mar;23(2):140-6. doi: 10.1016/j.etap.2006.08.003. Epub 2006 Aug 17.

Abstract

It is well known that developmental exposure to polychlorinated biphenyls (PCBs) could cause learning and memory deficits, but the underlying mechanisms are not clear. Actin cytoskeleton is directly involved in synaptic plasticity which is considered critical to learning and memory formation by LIM kinase 1 (LIMK-1)/cofilin pathway. To determine whether PCBs could alter actin cytoskeleton, we exposed the cultured hippocampal neurons to PCBs mixture Aroclor 1254 (A 1254). By biochemical measurement, fluorimetric assay and fluorescence microscopy, we found that A 1254 elicited a loss of filamentous actin, which preceded cytotoxicity. Western blots showed that a concentration-dependent decrease in the phosphorylation of cofilin and a decrease in LIMK-1 were induced by A 1254. We concluded that PCBs induced actin depolymerization in hippocampal neurons, probably by inhibiting the LIMK-1/cofilin signaling pathway. The above findings offer new perspectives for the understanding of PCBs-induced learning and memory deficits.

摘要

众所周知,发育过程中接触多氯联苯(PCBs)可能导致学习和记忆缺陷,但潜在机制尚不清楚。肌动蛋白细胞骨架直接参与突触可塑性,而突触可塑性被认为对学习和记忆的形成至关重要,这一过程是通过 LIM 激酶 1(LIMK-1)/丝切蛋白途径实现的。为了确定 PCBs 是否会改变肌动蛋白细胞骨架,我们将培养的海马神经元暴露于多氯联苯混合物 Aroclor 1254(A 1254)中。通过生化测量、荧光测定和荧光显微镜观察,我们发现 A 1254 引起丝状肌动蛋白的丧失,这先于细胞毒性。Western blot 显示,A 1254 诱导依赖于浓度的丝切蛋白磷酸化减少和 LIMK-1 减少。我们得出结论,PCBs 诱导海马神经元中的肌动蛋白解聚,可能是通过抑制 LIMK-1/丝切蛋白信号通路。上述发现为理解 PCBs 诱导的学习和记忆缺陷提供了新的视角。

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