title: NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation.
abstract: BACKGROUND
  Evidence from both clinical and experimental research indicates that the immune-brain interaction plays a pivotal role in the pathophysiology of depression. A multi-protein complex of the innate immune system, the NLRP3 inflammasome regulates cleavage and secretion of proinflammatory cytokine interleukin-1β. The inflammasome detects various pathogen-associated molecule patterns and damage-associated molecule patterns, which then leads to a series of immune-inflammatory reactions.
  
  
  METHODS
  To explore the role of inflammasome activation in the underlying biological mechanisms of depression, we established a mouse model of depression with unpredictable chronic mild stress.
  
  
  RESULTS
  Mice subjected to chronic mild stress for 4 weeks had significantly higher serum corticosterone levels, serum interleukin-1β levels, and hippocampal active interleukin-1β protein levels. They also displayed depressive-like symptoms, including decreased sucrose preference and increased immobility time. Moreover, the hippocampi of chronic mild stress-exposed mice had significantly higher activity of caspase-1, which accompanied by higher protein levels of NLRP3 and the apoptotic speck-containing protein with a card. Pretreatment with the NLRP3 inflammasome inhibitor VX-765 decreased serum and hippocampal levels of interleukin-1β protein and significantly moderated the depressive-like behaviors induced by chronic mild stress.
  
  
  CONCLUSIONS
  These data suggest the NLRP3 inflammasome mediates stress-induced depression via immune activation. Future procedures targeting the NLRP3 inflammasome may have promising effects in the prevention and treatment of depression.
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Yun-Zi
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Shen
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Teng-Yun
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health (Drs Y. Zhang, L. Liu, Y.-Z. Liu, X.-L. Shen, T.-Y. Wu, W. Wang, Y.-X. Wang, and C.-L. Jiang) and Department of Naval Aviation Medicine (Dr T. Zhang), Second Military Medical University, Shanghai, China. cljiang@vip.163.com cloudywang66@163.com.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D019422:Dietary Sucrose; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D005518:Food Preferences / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D035501:Uncertainty; D062366:para-Aminobenzoates / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D002352:Carrier Proteins; D019422:Dietary Sucrose; D004151:Dipeptides; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D062366:para-Aminobenzoates; C520022:belnacasan; D020170:Caspase 1; D003345:Corticosterone
keywords: NLRP3 inflammasome; depression; inflammation; interleukin-1β; stress