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Updated: Apr 18, 2026
A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation
Yi Zhang1, Lei Liu1, Yun-Zi Liu1
1Laboratory 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.
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.
