Abstract
The brominated flame retardant 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is widely distributed in the environment and poses a certain risk to human health. Studies have reported that oxidative stress is a key mechanism underlying BDE-47-induced neurotoxicity. Mitochondrial reactive oxygen species (mtROS) is a crucial mediator of NLRP3 inflammasome activation, which is involved in cognitive dysfunction induced by environmental toxins. However, the function of the mtROS-NLRP3 inflammasome pathway in BDE-47-elicited cognitive deficits and the underlying mechanisms remain elusive. Our data illustrated that eight weeks of BDE-47 (20 mg/kg) gavage led to cognitive deficits and hippocampal neuronal injury in mice. BDE-47 exposure downregulated Sirt3 expression and decreased the activity and expression level of SOD2, thereby inhibiting mtROS scavenging and activating NLRP3 inflammasome-mediated pyroptosis in the mouse hippocampus and BV-2 cells. In vitro, BDE-47-evoked microglial pyroptosis relied on NLRP3 inflammasome activation. Moreover, a mtROS scavenger (TEMPO) attenuated NLRP3 inflammasome activation and subsequent microglial pyroptosis under BDE-47 stress. Furthermore, Sirt3 overexpression restored the activity and expression of SOD2 and enhanced mtROS scavenging, thereby suppressing NLRP3 inflammasome activation and ameliorating microglial pyroptosis. Notably, honokiol (HKL), a pharmacological agonist of Sirt3, mitigated BDE-47-evoked hippocampal neuronal injury and cognitive impairment by inhibiting mtROS-NLRP3 axis-mediated pyroptosis via Sirt3 upregulation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.