Reduced NLRP3 inflammasome expression in the brain is associated with stress resilience

Yao Yang; Meng-Juan Xing; Yuan Li; Hui-Feng Zhang; Ti-Fei Yuan; Dai-Hui Peng

doi:10.1016/j.psyneuen.2021.105211

Reduced NLRP3 inflammasome expression in the brain is associated with stress resilience

Psychoneuroendocrinology. 2021 Jun:128:105211. doi: 10.1016/j.psyneuen.2021.105211. Epub 2021 Mar 26.

Authors

Yao Yang¹, Meng-Juan Xing², Yuan Li³, Hui-Feng Zhang⁴, Ti-Fei Yuan⁵, Dai-Hui Peng⁶

Affiliations

¹ Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key laboratory of Psychotic disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
² Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
³ Shanghai Key laboratory of Psychotic disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁴ Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁵ Shanghai Key laboratory of Psychotic disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China. Electronic address: [email protected].
⁶ Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].

PMID: 33812228
DOI: 10.1016/j.psyneuen.2021.105211

Abstract

Increased expression of the Nod-like receptor pyrin containing 3 (NLRP3) inflammasome and proinflammatory cytokines is associated with depressive behaviors. This study aimed to explore potential differences in neuroinflammation associated with stress resilience, as well as associated changes in autophagy, in a mouse model of chronic unpredictable mild stress (CUMS). Animals were classified as CUMS resilient or CUMS susceptible based on performance on behavioral tests following the CUMS protocol. Then the expression levels of NLRP3 inflammasome-related proteins, interleukin-1 beta (IL-1β), and Beclin 1 in stress-related brain regions (e.g., prefrontal cortex and hippocampus) were determined. Results showed that stress exposure triggered significant NLRP3 inflammasome increase in CUMS susceptible mice but not in CUMS resilient mice. These changes were accompanied by altered IL-1β and Beclin 1 expression levels. These findings indicate that stress resilience is associated with reduced pro-inflammatory signaling and autophagy activation, and suggest that therapeutically targeting these pathways might promote stress resilience.

Keywords: Beclin 1; Chronic unpredictable mild stress; Depression; Nod-like receptor pyrin containing 3 inflammasome; Stress resilience.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Beclin-1 / metabolism
Brain / metabolism*
Inflammasomes / metabolism*
Interleukin-1beta / metabolism
Male
Mice
Mice, Inbred C57BL
Models, Animal
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Neuroinflammatory Diseases / metabolism
Resilience, Psychological*
Stress, Psychological*

Substances

Beclin-1
IL1B protein, mouse
Inflammasomes
Interleukin-1beta
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse