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全氟辛烷磺酸 (PFOS) 对雄性小鼠认知行为和自噬的影响。

Effects of perfluorooctane sulfonate (PFOS) on cognitive behavior and autophagy of male mice.

机构信息

Institute of Advanced Pharmaceutical Technology, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, China.

Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, China.

出版信息

J Toxicol Sci. 2023;48(9):513-526. doi: 10.2131/jts.48.513.

Abstract

Perfluorooctane sulfonate (PFOS), an emerging environmental pollutant, is reported to cause neurotoxicity in animals and humans, but its underlying mechanisms are still unclear. We used in vivo models to investigate the effects of PFOS on cognition-related behaviors and related mechanisms. After 45 days of intragastric administration of PFOS (2 mg/kg or 8 mg/kg) in 7-week-old C57BL/6 mice, muscle strength, cognitive function and anxiety-like behavior were evaluated by a series of behavioral tests. The underling mechanisms of PFOS on impaired behaviors were evaluated by HE/Nissl staining, electron microscopy observation and western blot analysis. The results indicated that PFOS-exposed mice exhibited significant cognitive impairment, anxiety, neuronal degeneration and the abnormities of synaptic ultrastructure in the cortex and hippocampus. Western blot analysis indicated that PFOS exposure increased microtubule-associated protein light chain 3 (LC3) and decreased p62 protein levels, which may be associated with activation of autophagy leading to neuron damage. In summary, our results suggest that chronic exposure to PFOS adversely affects cognitive-related behavior in mice. These findings provide new mechanistic insights into PFOS-induced neurotoxicity.

摘要

全氟辛烷磺酸(PFOS)是一种新兴的环境污染物,据报道会对动物和人类造成神经毒性,但其潜在机制尚不清楚。我们使用体内模型研究了 PFOS 对认知相关行为的影响及其相关机制。在 7 周龄 C57BL/6 小鼠中经口给予 PFOS(2mg/kg 或 8mg/kg)45 天后,通过一系列行为测试评估肌肉力量、认知功能和焦虑样行为。通过 HE/Nissl 染色、电镜观察和 Western blot 分析评估 PFOS 对受损行为的潜在机制。结果表明,PFOS 暴露的小鼠表现出明显的认知障碍、焦虑、神经元变性以及皮质和海马突触超微结构的异常。Western blot 分析表明,PFOS 暴露增加了微管相关蛋白轻链 3(LC3)并降低了 p62 蛋白水平,这可能与自噬的激活导致神经元损伤有关。综上所述,我们的研究结果表明,慢性暴露于 PFOS 会对小鼠的认知相关行为产生不利影响。这些发现为 PFOS 诱导的神经毒性提供了新的机制见解。

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