Qi Mengjie, Wu Yue, Shi Han, Liu Jie, Zhu Run, Wang Jixiang, Rafique Amna, Yang Bo, Niu Ruiyan, Zhang Ding, Sun Zilong
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, 030801, Shanxi, PR China.
Biol Trace Elem Res. 2024 Oct 31. doi: 10.1007/s12011-024-04433-9.
Fluoride, an environmental toxicant, could induce endoplasmic reticulum stress (ERS) in neuronal cells ultimately leading to apoptosis and emotional dysfunction. Meanwhile, voluntary wheel running contributes to mitigate anxiety and depression. Our investigation aimed to study the effect of voluntary wheel running on anxiety- and depression-like behaviors in fluoride-exposure mice. The results showed that exposure to 100 mg/L sodium fluoride (NaF) for 6 months can induce anxiety- and depression-like behavior in mice. Fluorosis mice subjected to voluntary wheel running have less anxiety- and depression-like behaviors. Nissl and TUNEL staining demonstrated that fluoride led to a reduced proportion of Nissl body area in the cerebral cortex and an increased apoptotic ratio of nerve cells in the cerebral cortex. In contrast, these pathologic damages were improved in voluntary wheel running mice exposed to NaF. Moreover, the expressions of mRNA in the cerebral cortex GABA, GAD65, GAD67, DR, vGLU, 5-HT1A, BDNF, NMDAR1, and Bcl were downregulated and the levels of c-fos, GRP78, PERK, eIF2α, CHOP, Caspase-12, and Caspase-3 mRNA were upregulated in mice exposed to fluoride. NaF treatment had increased the PERK, ATF6, IRE1, p-eIF2α, and Caspase-3 protein levels and reduced the expressions of proteins, including GAD67, VGAT, BDNF, NMDAR1, PSD95, and SYN. By contrast, fluorosis mice subjected to voluntary wheel running enhanced the expression of GAD65, GAD67, VGAT, and neuroplasticity-related proteins in mice and inhibited the PERK-CHOP pathway. It is worth noting that the correlation between the amount of exercise and the behavioral indicators as well as neurotransmitter levels was found. In conclusion, voluntary wheel running inhibits the fluoride-induced ERS and GRP78 expression through the PERK-CHOP pathway and plays an anti-apoptotic role, ultimately ameliorating emotional dysfunction in NaF-exposed mice.
氟化物作为一种环境毒物，可诱导神经元细胞内质网应激（ERS），最终导致细胞凋亡和情绪功能障碍。同时，自愿性轮转运动有助于减轻焦虑和抑郁。我们的研究旨在探讨自愿性轮转运动对氟暴露小鼠焦虑样和抑郁样行为的影响。结果表明，暴露于100 mg/L氟化钠（NaF）6个月可诱导小鼠出现焦虑样和抑郁样行为。进行自愿性轮转运动的氟中毒小鼠的焦虑样和抑郁样行为较少。尼氏染色和TUNEL染色表明，氟化物导致大脑皮质中尼氏体面积比例降低，大脑皮质神经细胞凋亡率增加。相比之下，在暴露于NaF的自愿性轮转运动小鼠中，这些病理损伤得到改善。此外，暴露于氟化物的小鼠大脑皮质中GABA、GAD65、GAD67、DR、vGLU、5-HT1A、BDNF、NMDAR1和Bcl的mRNA表达下调，而c-fos、GRP78、PERK、eIF2α、CHOP、Caspase-12和Caspase-3 mRNA水平上调。NaF处理使PERK、ATF6、IRE1、p-eIF2α和Caspase-3蛋白水平升高，并降低了包括GAD67、VGAT、BDNF、NMDAR1、PSD95和SYN在内的蛋白质表达。相比之下，进行自愿性轮转运动的氟中毒小鼠增强了小鼠中GAD65、GAD67、VGAT和神经可塑性相关蛋白的表达，并抑制了PERK-CHOP通路。值得注意的是，发现了运动量与行为指标以及神经递质水平之间的相关性。总之，自愿性轮转运动通过PERK-CHOP通路抑制氟化物诱导的ERS和GRP78表达，并发挥抗凋亡作用，最终改善NaF暴露小鼠的情绪功能障碍。
