Ai Fujun, Wang Shengyuan, Ye Ling, Wan Wen, Zhou Xiao, Liu Minghai, Mo Kaiju, Lu Yongheng, Wei Na, Guan Zhizhong, Liu Yanjie
Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Pathology Morphology and Molecular Laboratory of the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Sci Rep. 2025 Aug 13;15(1):29760. doi: 10.1038/s41598-025-14631-7.
Prolonged exposure to fluoride may induce neurotoxic effects. Chondroitin sulfate (CS) exhibits protective functions within the central nervous system (CNS); however, the mechanism by which CS protects synapses against fluoride remains incompletely understood. Our objective was to investigate the protective efficacy of CS on synapses and decipher its underlying mechanisms. We showed that fluoride exposure reduced the expression of synaptic protein synaptophysin (SYN) and impaired learning and memory functions, whereas CS counteracted these alterations, suggesting its protective effect against fluoride-induced cognitive deficits. Further studies revealed disruption of the Erk1/2/MMP-2/MMP-9 signaling pathway both in vivo and in vitro, manifested by increased total Erk1/2, Erk1/2 phosphorylation and MMP-9 expression, along with decreased MMP-2 levels. Importantly, treatment of SH-SY5Y cells with PD98059 or CS attenuated fluoride-induced effects, indicating a regulatory role of CS in the Erk1/2/MMP-9 signaling pathway. However, MMP-2 was not implicated in this process. These data demonstrate the neuroprotective effects of CS and highlight its potential for protecting against fluoride-induced neurotoxicity and synaptic impairment.
长期接触氟化物可能会诱发神经毒性作用。硫酸软骨素（CS）在中枢神经系统（CNS）中具有保护功能；然而，CS保护突触免受氟化物影响的机制仍未完全清楚。我们的目的是研究CS对突触的保护作用并阐明其潜在机制。我们发现，氟化物暴露会降低突触蛋白突触素（SYN）的表达，并损害学习和记忆功能，而CS可抵消这些改变，表明其对氟化物诱导的认知缺陷具有保护作用。进一步的研究揭示了体内和体外Erk1/2/MMP-2/MMP-9信号通路的破坏，表现为总Erk1/2、Erk1/2磷酸化和MMP-9表达增加，同时MMP-2水平降低。重要的是，用PD98059或CS处理SH-SY5Y细胞可减弱氟化物诱导的效应，表明CS在Erk1/2/MMP-9信号通路中具有调节作用。然而，MMP-2未参与此过程。这些数据证明了CS的神经保护作用，并突出了其预防氟化物诱导的神经毒性和突触损伤的潜力。
