Niu 2018
| Data type(s) | Animal bioassay, In vitro |
|---|---|
| Full citation | Niu Q, Chen J, Xia T, Li P, Zhou G, Xu C, Zhao Q, Dong L, Zhang S, Wang A. 2018. Excessive ER stress and the resulting autophagic flux dysfunction contribute to fluoride-induced neurotoxicity. Environ Pollut 233: 889-899. |
| Abstract | Fluoride is capable of inducing neurotoxicity, but its mechanisms remain elusive. This study aimed to explore the roles of endoplasmic reticulum (ER) stress and autophagy in sodium fluoride (NaF)-induced neurotoxicity, focusing on the regulating role of ER stress in autophagy. The in vivo results demonstrated that NaF exposure impaired the learning and memory capabilities of rats, and resulted in histological and ultrastructural abnormalities in rat hippocampus. Moreover, NaF exposure induced excessive ER stress and associated apoptosis, as manifested by elevated IRE1α, GRP78, cleaved caspase-12 and cleaved-caspase-3, as well as defective autophagy, as shown by increased Beclin1, LC3-II and p62 expression in hippocampus. Consistently, the in vitro results further verified the findings of in vivo study that NaF induced excessive ER stress and defective autophagy in SH-SY5Y cells. Notably, inhibition of autophagy in NaF-treated SH-SY5Y cells with Wortmannin or Chloroquine decreased, while induction of autophagy by Rapamycin increased the cell viability. These results were correlated well with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in NaF-induced cell death. Importantly, mitigation of ER stress by 4-phenylbutyrate in NaF-treated SH-SY5Y cells inhibited the expressions of autophagy markers, and decreased cell apoptosis. Taken together, these data suggest that neuronal death resulted from excessive ER stress and autophagic flux dysfunction contributes to fluoride-elicited neurotoxicity. Moreover, the autophagic flux dysfunction was mediated by excessive ER stress, which provided novel insight into a better understanding of fluoride-induced neurotoxicity. |
| Reference hyperlink | |
| Literature review tags | Animal Study |
| COI reported | Authors report they have no COI |
| Funding source | Supported by grants from the State Key Program of National Natural Science of China (Grant No. 81430076), the National Natural Science Foundation of China (Grant No. 81273021), China Postdoctoral Science Foundation (Grant No. 2016T90694) and the Fundamental Research Funds for the Central Universities (HUST 2016YXMS221 and HUST 2015ZDTD052). |
| Study identifier | 32558 |
| Author contacted? | true |
| Author contact details | Author was contacted in September 2018 to obtain information for RoB assessment. |
| Summary/extraction comments | Figure 1 |
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Animal bioassay experiments
| Name | Type | Comments |
|---|---|---|
| 2-month water | Subchronic (30-90 days) | All the animals were housed under conditions of constant temperature (23-27 C) and humidity (55-60%) on 12-h light/dark cycles. Basal pellet diet and water were available ad libitum. Protocols involving animal experiments were appropriately approved by the Ethics Review Committee for Animal Research at Huazhong University of Science and Technology and were performed in strict accordance with guidelines for animal care. |