Inhibition of Microglial NLRP3 with MCC950 Attenuates Microglial Morphology and NLRP3/Caspase-1/IL-1β Signaling In Stress-induced Mice
| العنوان: | Inhibition of Microglial NLRP3 with MCC950 Attenuates Microglial Morphology and NLRP3/Caspase-1/IL-1β Signaling In Stress-induced Mice |
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| المؤلفون: | Qing Liu, Man-Man Zhang, Min-Xia Guo, Qiu-Ping Zhang, Na-Zhi Li, Jie Cheng, Shi-Le Wang, Guang-Hui Xu, Cheng-Fu Li, Ji-Xiao Zhu, Li-Tao Yi |
| المصدر: | Journal of Neuroimmune Pharmacology. 17:503-514 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, Immunology, Neuroscience (miscellaneous), Immunology and Allergy |
| الوصف: | Major depressive disorder is characterized by the deficiencies of monoamine neurotransmitters, neurotrophic factors and persistent neuroinflammation. Microglial activation has been associated with neuroinflammation-related mental diseases, accompanied by NLR family pyrin domain containing 3 (NLRP3) inflammasome. Here, we investigated the effect of NLRP3 inhibition by its small molecular inhibitor MCC950 on inflammatory activity and depressive-like mice induced by chronic unpredictable mild stress (CUMS), followed by the behavioral tests including sucrose preference test and forced swimming test. NLRP3/caspase-1/IL-1β signaling and microglial morphology in the prefrontal cortex were measured. The results showed that CUMS caused a decrease in sucrose preference and an increase in immobility time, which were reversed by NLRP3 inhibitor MCC950. In addition, NLRP3 inhibition decreased the number of microglia and changed the activated state of microglia to a resting state by morphology 3D reconstruction. Moreover, NLRP3 inhibition inactivated NLRP3/caspase-1/IL-1β signaling in the prefrontal cortex. The results from immunofluorescence demonstrated that NLRP3 and IL-1β expression was decreased in microglia in response to MCC950 treatment. Accordingly, proinflammatory cytokines were also decreased by NLRP3 inhibition. In conclusion, this study demonstrates that microglial NLRP3 inhibition prevents stress-induced neuroinflammation in the prefrontal cortex and suggests that microglial NLRP3 could be one of the potential therapeutic targets for depression treatment. |
| تدمد: | 1557-1904 1557-1890 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2073dd0fd658c7a051c1b9841aead390 https://doi.org/10.1007/s11481-021-10037-0 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....2073dd0fd658c7a051c1b9841aead390 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15571904 15571890 |
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