香芹酚
神经发生
干预(咨询)
氟化物
化学
药理学
生物
神经科学
医学
食品科学
精神科
无机化学
精油
作者
Yuhui Du,Zichen Feng,Minghui Gao,Anqi Wang,Xi Yan,Ruiqin Chen,Bin Liu,Fangfang Yu,Yue Ba,Guoyu Zhou
标识
DOI:10.1016/j.envpol.2024.124371
摘要
The negative regulation on neurogenesis has been implicated in fluoride neurotoxicity, while the evidence is limited. To explore whether fluoride interferes with neurogenesis via the Notch1 signaling and the potential alleviation effects of carvacrol (CAR), we conducted in vivo and in vitro experiments, as well as epidemiological analyses in this study. The results showed that urinary fluoride levels and circulating Notch1 levels were associated with IQ levels in boys. NaF-treated rats had fewer neurons, lower densities of dendritic spines, depressed neurogenesis, and impaired learning and memory abilities. In vitro experiments using undifferentiated PC12 cells mimicking neurogenesis revealed that NaF suppressed differentiation and neurite outgrowth. Besides, Notch1 signaling activation was detected in vivo and in vitro. The latter was confirmed using an in vitro model supplemented with DAPT, a potent Notch1 inhibitor. Furthermore, CAR supplementation negatively regulated NICD1 and Hes1 expressions and promoted hippocampal neurogenesis, thereby improving neurological functions in NaF-treated rats. These findings indicated that the inhibition of neurogenesis in hippocampi induced by fluoride via Notch1 signaling activation may be one of the underlying mechanisms of its neurotoxicity, and that CAR significantly alleviated the neurotoxicity of NaF via the Notch1 signaling.
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