Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice
Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.993405/full |
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| author | Yuxiang Jia Lele Tang Yu Yao Limin Zhuo Dongxiao Qu Xingxing Chen Yonghua Ji Jie Tao Yudan Zhu |
| author_facet | Yuxiang Jia Lele Tang Yu Yao Limin Zhuo Dongxiao Qu Xingxing Chen Yonghua Ji Jie Tao Yudan Zhu |
| author_sort | Yuxiang Jia |
| collection | DOAJ |
| description | Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities. |
| first_indexed | 2024-12-10T14:19:21Z |
| format | Article |
| id | doaj.art-b4c823e760094569b4ce12b568bb673b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-10T14:19:21Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-b4c823e760094569b4ce12b568bb673b2022-12-22T01:45:14ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-09-011310.3389/fneur.2022.993405993405Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in miceYuxiang Jia0Lele Tang1Yu Yao2Limin Zhuo3Dongxiao Qu4Xingxing Chen5Yonghua Ji6Jie Tao7Yudan Zhu8School of Medicine, Shanghai University, Shanghai, ChinaDepartment of Neurology and Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Medicine, Shanghai University, Shanghai, ChinaSchool of Medicine, Shanghai University, Shanghai, ChinaDepartment of Neurology and Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Neurology and Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Medicine, Shanghai University, Shanghai, ChinaDepartment of Neurology and Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Neurology and Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities.https://www.frontiersin.org/articles/10.3389/fneur.2022.993405/fullseizureslow-intensity exercisesodium valproateco-morbiditiesTLR4/NF-κB pathwayinflammatory factors |
| spellingShingle | Yuxiang Jia Lele Tang Yu Yao Limin Zhuo Dongxiao Qu Xingxing Chen Yonghua Ji Jie Tao Yudan Zhu Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice Frontiers in Neurology seizures low-intensity exercise sodium valproate co-morbidities TLR4/NF-κB pathway inflammatory factors |
| title | Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice |
| title_full | Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice |
| title_fullStr | Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice |
| title_full_unstemmed | Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice |
| title_short | Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice |
| title_sort | low intensity exercise combined with sodium valproate attenuates kainic acid induced seizures and associated co morbidities by inhibiting nf κb signaling in mice |
| topic | seizures low-intensity exercise sodium valproate co-morbidities TLR4/NF-κB pathway inflammatory factors |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.993405/full |
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