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Journal of Neuroinflammation

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01-12-2020 | Mood Disorders | Research

NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice

Authors: Ao-Qi Song, Bo Gao, Jun-Juan Fan, Ya-Jing Zhu, Jun Zhou, Yu-Ling Wang, Li-Zhong Xu, Wen-Ning Wu

Published in: Journal of Neuroinflammation | Issue 1/2020

Abstract

Background

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression.

Methods

Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion.

Results

Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus.

Conclusions

NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.

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Title: NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice
Authors: Ao-Qi Song
Bo Gao
Jun-Juan Fan
Ya-Jing Zhu
Jun Zhou
Yu-Ling Wang
Li-Zhong Xu
Wen-Ning Wu
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Mood Disorders
Affective Disorder
Published in: Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-020-01848-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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