Main content area

Aluminum trichloride caused hippocampal neural cells death and subsequent depression-like behavior in rats via the activation of IL-1β/JNK signaling pathway

Zhang, Haiyang, Wei, Mian, Lu, Xiangyu, Sun, Qinghong, Wang, Chuqiao, Zhang, Jiuyan, Fan, Honggang
The Science of the total environment 2020 v.715 pp. 136942
aluminum, aluminum chloride, apoptosis, caspase-3, caspase-8, death, enzyme activity, gene expression, gene expression regulation, genes, hippocampus, histopathology, interleukin-1beta, messenger RNA, mitogen-activated protein kinase, necroptosis, neurodegenerative diseases, neurons, oral exposure, phosphorylation, pollutants, protein content, protein synthesis, proteins, rats, signal transduction, tumor necrosis factor-alpha
Aluminum (Al) is an inorganic pollutant that induces nerve cells apoptosis and necroptosis, thereby causing depression and neurodegenerative diseases. IL-1β/JNK signaling pathway can regulate apoptosis and necroptosis. However, it remains unclear whether IL-1β/JNK signaling pathway is involving in the regulation of Al-induced hippocampal neural cells apoptosis and necroptosis. To investigate the mechanism of Al on neural cells apoptosis and necroptosis, rats were orally exposed to different doses of AlCl₃ for 90 days. The open-field test results showed that AlCl₃ caused depressive behavior in rats. Histopathological evidence showed that AlCl₃ induced hippocampal neural cells apoptosis and necrosis. Moreover, Bax/Bcl-2 mRNA expression ratio, caspase-3 activity and mRNA expression and TUNEL positive rates were upregulated, meanwhile, TNF-α mRNA and protein expression levels, TNFR1, RIP1, RIP3 and MLKL proteins levels were increased, while caspase-8 protein level was decreased in the hippocampus of Al-exposed groups. These results proved that AlCl₃ induced hippocampal neural cells apoptosis and necroptosis. Combined with histopathology and correlation analysis, we deduced that hippocampal neural cells were more likely to undergo necroptosis at high doses (450 mg/kg) of AlCl₃, while <150 mg/kg AlCl₃ tended to induce apoptosis. Finally, AlCl₃ increased the proteins level of IL-1β, IL-1RI, IL-1RAcP, JNK and p-JNK, indicating that AlCl₃ activated IL-1β/JNK signaling pathway. However, the application of IL-1 receptor antagonist (IL-1Ra) inhibited the phosphorylation of JNK and the related genes expression of apoptosis and necroptosis caused by AlCl₃. Thus, we concluded that AlCl₃ induced hippocampal neural cells death and depression-like behavior in rats by activating IL-1β/JNK signaling pathway.