Microglia nuclear receptor corepressor 1 deficiency alleviates neuroinflammation in mice

• Published in: Neuroscience letters 2024-02, Vol.822, p.137643-137643, Article 137643
• Main Authors: Qiu, Shuqin, Xian, Zihong, Chen, Junyu, Huang, Peng, Wang, Honghao, Wang, Haitao, Xu, Jiangping
• Format: Article
• Language: English
• Subjects: LPS; Microglia; NCoR1; PGC-1α
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2024.137643

•The expression and location of NCoR1 were affected after lipopolysaccharide (LPS) stimulation in BV2 cells.•Microglia-specific NCoR1 knockout mice ameliorated LPS-induced anhedonia, locomotor activity and cognitive dysfunction.•The lack of NCoR1 alleviated neuroinflammation possibly attributable to the increased expression of PGC-1α. Given the established role of nuclear receptor corepressor 1 (NCoR1) in sensing environmental cues and the importance of inflammation in neurodegenerative diseases, elucidation of NCoR1 involvement in neuroinflammation has notable implications. Yet, its regulatory mechanism remains largely unclear. Under in vitro conditions, NCoR1 expression peaked and then decreased at 12 h after lipopolysaccharides (LPS) stimulation in BV2 cells, However, NCoR1 knockdown using si-RNA attenuated microglial inflammation, evident by reduced the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), phosphorylated-JNK and high mobility group box-1 (HMGB1). Furthermore, NCoR1 suppression could counteract the decline in mitochondrial membrane potential while simultaneously enhancing the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Under in vivo conditions, microglia-specific NCoR1 knockout (MNKO) mice after LPS injections alleviated the symptoms of anhedonia, diminished autonomic activity and cognitive impairment. Additionally, MNKO mice showed attenuation of microglial activation, downregulated HMGB1 and COX2, and upregulated PGC-1α expression in the cortex. In conclusion, these findings suggest that NCoR1 deficiency leads to a modest reduction in neuroinflammation, possibly attributed to the increased expression of PGC-1α.