P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine
Abstract Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. Howe...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-022-01442-8 |
| _version_ | 1811328463201632256 |
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| author | Yajuan Wang Zhengming Shan Lily Zhang Shanghua Fan Yanjie Zhou Luyu Hu Yue Wang Weidong Li Zheman Xiao |
| author_facet | Yajuan Wang Zhengming Shan Lily Zhang Shanghua Fan Yanjie Zhou Luyu Hu Yue Wang Weidong Li Zheman Xiao |
| author_sort | Yajuan Wang |
| collection | DOAJ |
| description | Abstract Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1β and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine. |
| first_indexed | 2024-04-13T15:26:40Z |
| format | Article |
| id | doaj.art-4febc1dd27734a148f77db644ed5488a |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-04-13T15:26:40Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-4febc1dd27734a148f77db644ed5488a2022-12-22T02:41:30ZengBMCThe Journal of Headache and Pain1129-23691129-23772022-07-0123112310.1186/s10194-022-01442-8P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraineYajuan Wang0Zhengming Shan1Lily Zhang2Shanghua Fan3Yanjie Zhou4Luyu Hu5Yue Wang6Weidong Li7Zheman Xiao8Department of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityAbstract Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1β and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine. https://doi.org/10.1186/s10194-022-01442-8MigraineCognitive impairmentP2X7 receptorNLRP3 inflammasomePyroptosisApoptosis |
| spellingShingle | Yajuan Wang Zhengming Shan Lily Zhang Shanghua Fan Yanjie Zhou Luyu Hu Yue Wang Weidong Li Zheman Xiao P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine The Journal of Headache and Pain Migraine Cognitive impairment P2X7 receptor NLRP3 inflammasome Pyroptosis Apoptosis |
| title | P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| title_full | P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| title_fullStr | P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| title_full_unstemmed | P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| title_short | P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| title_sort | p2x7r nlrp3 signaling pathway mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine |
| topic | Migraine Cognitive impairment P2X7 receptor NLRP3 inflammasome Pyroptosis Apoptosis |
| url | https://doi.org/10.1186/s10194-022-01442-8 |
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