NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors
Major depressive disorder is one of the most common psychiatric disorders, and the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in depression. Dorsal raphe nucleus (DRN), as the main origin of producing serotonin in the brain, is an important functi...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025002175 |
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| author | Junchao Cai Jiarong Zhao Rui Peng Heming Yu Yong He Qigang Zhou Yue Wang Peng Xie |
| author_facet | Junchao Cai Jiarong Zhao Rui Peng Heming Yu Yong He Qigang Zhou Yue Wang Peng Xie |
| author_sort | Junchao Cai |
| collection | DOAJ |
| description | Major depressive disorder is one of the most common psychiatric disorders, and the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in depression. Dorsal raphe nucleus (DRN), as the main origin of producing serotonin in the brain, is an important functional brain region in depressive disorders. However, the relationship between NLRP3 in the DRN and depression has not been clarified in previous studies. So, we focus on demonstrating the role of NLRP3 expressed in DRN in depression. In this study, the male C57BL/6 J mice were exposed to chronic unpredictable mild stimulation and the expression and cellular localization of NLRP3 in DRN were analyzed. Subsequently, the mice were treated with the NLRP3 inhibitor MCC950 to inhibit NLRP3 inflammasome, and the expression of NLRP3 was knocked down in certain cells within the DRN of NLRP3fl/fl mice to investigate the role of NLRP3 in regulating depressive phenotype. Compared with the control group, the expression of NLRP3 in DRN of CUMS group was significantly increased, especially in the microglia and neuron. Furthermore, treatment with the NLRP3 inhibitor induced a significant antidepressant effect, and the depressive phenotype of NLRP3fl/fl mice was rescued after knocking down NLRP3 in the microglia or neuron. In addition, the expression levels of related molecules in the NLRP3 inflammasome pathway were significantly higher in the CUMS group compared to the control group. These results illustrated that NLRP3 played an important role in regulating depressive phenotype in DRN, and suggested a new therapy target for depression. |
| format | Article |
| id | doaj-art-29cbbc2f9d5a46399ea9948f132dbd3a |
| institution | OA Journals |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-29cbbc2f9d5a46399ea9948f132dbd3a2025-08-20T02:31:33ZengElsevierBrain Research Bulletin1873-27472025-07-0122711140510.1016/j.brainresbull.2025.111405NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviorsJunchao Cai0Jiarong Zhao1Rui Peng2Heming Yu3Yong He4Qigang Zhou5Yue Wang6Peng Xie7Department of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaState Key Laboratory of Reproductive Medicine, Department of Clinic Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Corresponding author.Department of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Chongqing Institute for Brain and Intelligence, Chongqing 401336, China; Corresponding author at: Department of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaMajor depressive disorder is one of the most common psychiatric disorders, and the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in depression. Dorsal raphe nucleus (DRN), as the main origin of producing serotonin in the brain, is an important functional brain region in depressive disorders. However, the relationship between NLRP3 in the DRN and depression has not been clarified in previous studies. So, we focus on demonstrating the role of NLRP3 expressed in DRN in depression. In this study, the male C57BL/6 J mice were exposed to chronic unpredictable mild stimulation and the expression and cellular localization of NLRP3 in DRN were analyzed. Subsequently, the mice were treated with the NLRP3 inhibitor MCC950 to inhibit NLRP3 inflammasome, and the expression of NLRP3 was knocked down in certain cells within the DRN of NLRP3fl/fl mice to investigate the role of NLRP3 in regulating depressive phenotype. Compared with the control group, the expression of NLRP3 in DRN of CUMS group was significantly increased, especially in the microglia and neuron. Furthermore, treatment with the NLRP3 inhibitor induced a significant antidepressant effect, and the depressive phenotype of NLRP3fl/fl mice was rescued after knocking down NLRP3 in the microglia or neuron. In addition, the expression levels of related molecules in the NLRP3 inflammasome pathway were significantly higher in the CUMS group compared to the control group. These results illustrated that NLRP3 played an important role in regulating depressive phenotype in DRN, and suggested a new therapy target for depression.http://www.sciencedirect.com/science/article/pii/S0361923025002175DepressionNLRP3Dorsal raphe nucleusInflammation |
| spellingShingle | Junchao Cai Jiarong Zhao Rui Peng Heming Yu Yong He Qigang Zhou Yue Wang Peng Xie NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors Brain Research Bulletin Depression NLRP3 Dorsal raphe nucleus Inflammation |
| title | NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors |
| title_full | NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors |
| title_fullStr | NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors |
| title_full_unstemmed | NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors |
| title_short | NLRP3 in the dorsal raphe nucleus manipulates the depressive-like behaviors |
| title_sort | nlrp3 in the dorsal raphe nucleus manipulates the depressive like behaviors |
| topic | Depression NLRP3 Dorsal raphe nucleus Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025002175 |
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