CY-09 Alleviates the Depression-like Behaviors via Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation in Lipopolysaccharide-Induced Mice

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considere...

Full description

Saved in:
Bibliographic Details
Published in:ACS chemical neuroscience 2022-12, Vol.13 (23), p.3291-3302
Main Authors: Wang, Yu, Liu, Yi-Jie, Zhang, Man-Man, Zhou, Han, Gao, Yi-Han, Cheng, Wen-Jing, Ye, Zi-Wei, Yuan, Zhong-Yu, Xu, Guang-Hui, Li, Cheng-Fu, Yi, Li-Tao
Format: Article
Language:English
Subjects:
Animals
Depression - drug therapy
Depression - etiology
Hippocampus - drug effects
Hippocampus - metabolism
Inflammasomes - drug effects
Lipopolysaccharides - toxicity
Mice
Neuroinflammatory Diseases - complications
NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
Thiazolidines - pharmacology
Thiazolidines - therapeutic use
Thiones - pharmacology
Thiones - therapeutic use
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considered to be involved in the pathophysiology of depression. In this study, the putative role of CY-09, a selective and direct inhibitor of NLRP3, was evaluated in the lipopolysaccharide (LPS)-induced mice. The results of the study indicated that CY-09 significantly decreased the levels of NLRP3 in the hippocampus of LPS-induced mice. In addition, CY-09 increased the sucrose preference and shortened the immobility time in LPS-induced mice, suggesting the antidepressant-like effects of inhibiting NLRP3 inflammasome. Biochemical analysis showed that LPS significantly activated the NLRP3/ASC/cytokine signaling pathway and caused microglial activation, while CY-09 prevented the changes. Moreover, CY-09 increased the brain-derived neurotrophic factor (BDNF) only in microglia but not in the whole hippocampus. Meanwhile, CY-09 did not promote neurogenesis in the hippocampus of LPS mice. In conclusion, the results of the study showed that the antidepressant-like effects of NLRP3 inhibitor CY-09 were mediated by alleviating neuroinflammation in microglia and independent of the neurotrophic function in the hippocampus.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.2c00348