Hydrogen Sulfide Prevents LPS-Induced Depression-like Behavior through the Suppression of NLRP3 Inflammasome and Pyroptosis and the Improvement of Mitochondrial Function in the Hippocampus of Mice.
Peng BaoYuxiang GongYanjie WangMiaomiao XuZhenyu QianXin NiJianqiang LuPublished in: Biology (2023)
Hydrogen sulfide (H 2 S) has been implicated to have antidepressive effects. We sought to investigate the prevention effects of H 2 S donor NaHS on depression-like behavior induced by lipopolysaccharide (LPS) in mice and its potential mechanisms. Sucrose preference, force swimming, open field, and elevate zero maze were used to evaluate depression-like behavior. NF-κB and NLRP3 inflammasome activation and mitochondrial function in the hippocampus were determined. It was found that depression-like behavior induced by LPS was prevented by NaHS pretreatment. LPS caused NF-κB and NLRP3 inflammasome activation in the hippocampus as evidenced by increased phosphorylated-p65 levels and increased NLRP3, ASC, caspase-1, and mature IL-1β levels in the hippocampus, which were also blocked by NaHS. LPS increased GSDMD-N levels and TUNEL-positive cells in the hippocampus, which was prevented by NaHS. Abnormal mitochondrial morphology in the hippocampus was found in LPS-treated mice. Mitochondrial membrane potential and ATP production were reduced, and ROS production was increased in the hippocampus of LPS-treated mice. NaHS pretreatment improved impaired mitochondrial morphology and increased membrane potential and ATP production and reduced ROS production in the hippocampus of LPS-treated mice. Our data indicate that H 2 S prevents LPS-induced depression-like behaviors by inhibiting NLRP3 inflammasome activation and pyroptosis and improving mitochondrial function in the hippocampus.
Keyphrases
- nlrp inflammasome
- lps induced
- inflammatory response
- prefrontal cortex
- cerebral ischemia
- cognitive impairment
- depressive symptoms
- toll like receptor
- high fat diet induced
- anti inflammatory
- oxidative stress
- signaling pathway
- induced apoptosis
- subarachnoid hemorrhage
- pi k akt
- adipose tissue
- metabolic syndrome
- nuclear factor
- mouse model
- electronic health record
- cell proliferation
- physical activity
- artificial intelligence
- machine learning
- wild type
- immune response
- reactive oxygen species
- human health