Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice

作者：Yajing Zhu, Jing Huang, Ru Chen, Yu Zhang, Xin He, Wen-Xin Duan, Yuan-Lei Zou, Meng-Mei Sun, Huili Sun, Si-Min Cheng, Hao‐Chuan Wang, Hao Zhang, Wen‐Ning Wu · 发表于：Journal of Neuroinflammation · 年份：2024 · DOI：10.1186/s12974-023-02995-4 · 被引用次数：45 · 研究领域：Tryptophan and brain disorders、Inflammasome and immune disorders、Autophagy in Disease and Therapy

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autop...