Chronic aerosol inhalation of arsenic and cadmium induces dopaminergic neuron loss in mouse striatum via NF-κB/NLRP3 signaling pathway
Objective The neuropathological characteristics of striatum of mice chronically exposed to arsenic and cadmium by aerosol inhalation were characterized in situ,and the pathological mechanism was investigated from the oxidative stress-NF-κb/NLRP3 pathway.Methods 8-week-old C57BL/6J male mice were selected and divided into control group(n=6),sodium arsenite atomization inhalation group(n=6)and cadmium chloride atomization inhalation group(n=4).The mice were subjected to ultrasonic atomization inhalation of double deionized water,6 mg/kg sodium arsenite solution and 10 mg/kg cadmium chloride solution respectively for 4 h every day,lasting for 6 months.Mouse brains were extracted under anesthesia.The pathological changes of striatum were observed by HE staining and Nissl staining.The levels of 8-hydroxy-deoxyguanosine(8-OHdG),tyrosine hydroxylase(TH),p-NF-κB-p65 and NLRP3 were detected by immunohistochemical method.The activation of astrocytes and microglia was detected by GFAP co-labeled with C3 and Iba-1 co-labeled with CD68 by immunofluorescence staining.Results Compared with the control group,more neurons were damaged in the striatum in the arsenic and cadmium atomization inhalation groups(Nissl staining:tAs=4.920,tCd=6.185,P＜0.01;HE staining:tAs=4.150,tCd=6.761,P＜0.01),TH levels decreased(tAs=2.145,tCd=4.603,P＜0.05 or P＜0.01),the levels of 8-OHdG,p-NF-κB-p65 and NLRP3 increased(8-OHdG:tAs=3.993,tCd=2.396,P＜0.01 or P＜0.05;p-NF-κB-p65:tAs=7.117,tCd=9.352,P＜0.01;NLRP3:tAs=6.967,tCd=7.306,P＜0.01),the ratios of inflammatory activated A1 astrocytes and M1 microglia increased significantly(A1 astrocytes:tAs=4.586,tCd=3.003,P＜0.01 or P＜0.05;M1 microglia:tAs=6.135,tCd=6.245,P＜0.05).Conclusion Inhalation exposure to arsenic and cadmium can damage striatal dopaminergic neurons,and the mechanism may be related to the activation of NF-κB/NLRP3 inflammasome pathway by inducing oxidative stress and causing inflammatory response of glial cells.
NETL
NSTL
万方数据
