NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction
As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323003329 |
| _version_ | 1797851998207344640 |
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| author | Xiaozheng Zhu Huiping Liu Diya Wang Ruili Guan Yuankang Zou Ming Li Jianbin Zhang Jingyuan Chen |
| author_facet | Xiaozheng Zhu Huiping Liu Diya Wang Ruili Guan Yuankang Zou Ming Li Jianbin Zhang Jingyuan Chen |
| author_sort | Xiaozheng Zhu |
| collection | DOAJ |
| description | As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4. |
| first_indexed | 2024-04-09T19:26:57Z |
| format | Article |
| id | doaj.art-a7af74b98e6f4f57b234c7df22306d67 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-09T19:26:57Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-a7af74b98e6f4f57b234c7df22306d672023-04-05T08:05:56ZengElsevierEcotoxicology and Environmental Safety0147-65132023-04-01255114828NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunctionXiaozheng Zhu0Huiping Liu1Diya Wang2Ruili Guan3Yuankang Zou4Ming Li5Jianbin Zhang6Jingyuan Chen7Tianjin Institute of Environmental and Operational Medicine, ChinaSchool of Medicine, Quzhou College of Technology, ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, China; Correspondence to: Tianjin Institute of Environmental and Operational Medicine, No.1 Dali Road, Tianjin 300050, China.Tianjin Institute of Environmental and Operational Medicine, China; Correspondence to: Tianjin Institute of Environmental and Operational Medicine, No.1 Dali Road, Tianjin 300050, China.As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.http://www.sciencedirect.com/science/article/pii/S0147651323003329HypoxiaNLRP3 inflammasomeNeuroinflammationNeuronal lossCognitive dysfunction |
| spellingShingle | Xiaozheng Zhu Huiping Liu Diya Wang Ruili Guan Yuankang Zou Ming Li Jianbin Zhang Jingyuan Chen NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction Ecotoxicology and Environmental Safety Hypoxia NLRP3 inflammasome Neuroinflammation Neuronal loss Cognitive dysfunction |
| title | NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| title_full | NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| title_fullStr | NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| title_full_unstemmed | NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| title_short | NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| title_sort | nlrp3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction |
| topic | Hypoxia NLRP3 inflammasome Neuroinflammation Neuronal loss Cognitive dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323003329 |
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