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Aluminum trichloride caused hippocampal neural cells death and subsequent depression-like behavior in rats via the activation of IL-1β/JNK signaling pathway.
Science of the Total Environment ( IF 8.2 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.scitotenv.2020.136942 Haiyang Zhang 1 , Mian Wei 1 , Xiangyu Lu 1 , Qinghong Sun 2 , Chuqiao Wang 1 , Jiuyan Zhang 1 , Honggang Fan 1
Science of the Total Environment ( IF 8.2 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.scitotenv.2020.136942 Haiyang Zhang 1 , Mian Wei 1 , Xiangyu Lu 1 , Qinghong Sun 2 , Chuqiao Wang 1 , Jiuyan Zhang 1 , Honggang Fan 1
Affiliation
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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.
中文翻译：
三氯化铝通过激活IL-1β/ JNK信号通路导致大鼠海马神经细胞死亡和随后的抑郁样行为。
铝（Al）是一种无机污染物，可诱导神经细胞凋亡和坏死性硬化，从而引起抑郁和神经退行性疾病。IL-1β/ JNK信号通路可以调节细胞凋亡和坏死性坏死。然而，目前尚不清楚IL-1β/ JNK信号通路是否参与调节铝诱导的海马神经细胞凋亡和坏死性坏死。为了研究Al对神经细胞凋亡和坏死性坏死的机制，将大鼠口服不同剂量的AlCl3 90天。野外试验结果表明，AlCl3引起了大鼠的抑郁行为。组织病理学证据表明，AlCl3诱导海马神经细胞凋亡和坏死。此外，Bax / Bcl-2 mRNA表达比率，caspase-3活性和mRNA表达以及TUNEL阳性率均被上调，与此同时，铝暴露组海马中TNF-αmRNA和蛋白表达水平，TNFR1，RIP1，RIP3和MLKL蛋白水平升高，而caspase-8蛋白水平降低。这些结果证明AlCl 3诱导海马神经细胞凋亡和坏死。结合组织病理学和相关分析，我们推断高剂量（450 mg / kg）AlCl3时海马神经细胞更容易发生坏死病，而＜150 mg / kg AlCl3则倾向于诱导凋亡。最后，AlCl3增加了IL-1β，IL-1RI，IL-1RAcP，JNK和p-JNK的蛋白水平，表明AlCl3激活了IL-1β/ JNK信号通路。然而，IL-1受体拮抗剂（IL-1Ra）的应用抑制了JNK的磷酸化以及由AlCl3引起的凋亡和坏死性坏死相关基因的表达。从而，
更新日期：2020-01-26
中文翻译：
三氯化铝通过激活IL-1β/ JNK信号通路导致大鼠海马神经细胞死亡和随后的抑郁样行为。
铝（Al）是一种无机污染物，可诱导神经细胞凋亡和坏死性硬化，从而引起抑郁和神经退行性疾病。IL-1β/ JNK信号通路可以调节细胞凋亡和坏死性坏死。然而，目前尚不清楚IL-1β/ JNK信号通路是否参与调节铝诱导的海马神经细胞凋亡和坏死性坏死。为了研究Al对神经细胞凋亡和坏死性坏死的机制，将大鼠口服不同剂量的AlCl3 90天。野外试验结果表明，AlCl3引起了大鼠的抑郁行为。组织病理学证据表明，AlCl3诱导海马神经细胞凋亡和坏死。此外，Bax / Bcl-2 mRNA表达比率，caspase-3活性和mRNA表达以及TUNEL阳性率均被上调，与此同时，铝暴露组海马中TNF-αmRNA和蛋白表达水平，TNFR1，RIP1，RIP3和MLKL蛋白水平升高，而caspase-8蛋白水平降低。这些结果证明AlCl 3诱导海马神经细胞凋亡和坏死。结合组织病理学和相关分析，我们推断高剂量（450 mg / kg）AlCl3时海马神经细胞更容易发生坏死病，而＜150 mg / kg AlCl3则倾向于诱导凋亡。最后，AlCl3增加了IL-1β，IL-1RI，IL-1RAcP，JNK和p-JNK的蛋白水平，表明AlCl3激活了IL-1β/ JNK信号通路。然而，IL-1受体拮抗剂（IL-1Ra）的应用抑制了JNK的磷酸化以及由AlCl3引起的凋亡和坏死性坏死相关基因的表达。从而，
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