Effect of artesunate on neuroinflammation in depressed mouse model by regulating cGAS-STING signaling pathway
10.16352/j.issn.1001-6325.2024.08.1126
- VernacularTitle:青蒿琥酯调节cGAS-STING信号通路对抑郁症模型小鼠神经炎性反应的影响
- Author:
Chao GAO
1
;
Runhan ZHANG
;
Wei WANG
;
Manting ZHAO
;
Yan JIAO
;
Zhe LI
Author Information
1. 沧州市中心医院儿童保健科,河北沧州 061000
- Keywords:
artesunate;
cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway;
depression;
inflammation;
apoptosis
- From:
Basic & Clinical Medicine
2024;44(8):1126-1132
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of artesunate(ART)on neuroinflammation in depressed mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon gene(STING)pathway.Methods Mice were divided into model group,control group,low-dose ART group,high-dose ART group,fluoxetine group,and high-dose ART+RocA(cGAS-STING pathway activator)group.Sugar solution consumption experiment and forced swimming experiment were applied to evaluate the depressive behavior of mice;HE staining microscopy was applied to detect pathological changes in hippocampal tissue;ELISA method was applied to detect the level of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),serotonin(5-HT)and dopa-mine(DA);TUNEL staining microscopy was applied to detect neuronal apoptosis;Western blot was applied to detect Bcl-2 associated X protein(Bax),p53,cGAS,and STING proteins.Results Compared to the control group,the mice in the model group exhibited neuronal pustule degeneration,the sugar water consumption rate,level of 5-HT and DA decreased,the rest time of forced swimming increased.The level of IL-6 and TNF-α,neuronal apoptosis rate,expression of Bax,p53,cGAS,and STING proteins all elevated(P＜0.05);Compared with model group,the damage to hippocampus neurons in the ART low-dose group,ART high-dose group and fluoxetine group neuronal pus-tular degeneration was alleviated,while sugar water consumption rate,5-HT,and DA levels increased,the rest time of forced swimming reduced,the level of IL-6 and TNF-α,neuronal apoptosis rate and the expression of Bax,p53,cGAS,and STING proteins reduced(P＜0.05);RocA reversed the improvement effect of high-dose ART on depression in mice.Conclusions ART inhibits neuroinflammation and neuronal apoptosis in depressed mice,and up-regulates amine neurotransmitters expression.The mechanism is potentially related to the blocking of cGAS-STING pathway.
