Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice
Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive imp...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.620176/full |
| _version_ | 1818741994446389248 |
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| author | Yanmin Chang Yi Yao Rong Ma Zemin Wang Junjie Hu Yanqing Wu Xingjun Jiang Lulu Li Gang Li |
| author_facet | Yanmin Chang Yi Yao Rong Ma Zemin Wang Junjie Hu Yanqing Wu Xingjun Jiang Lulu Li Gang Li |
| author_sort | Yanmin Chang |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD. |
| first_indexed | 2024-12-18T02:05:28Z |
| format | Article |
| id | doaj.art-2e2fef0bac994271859537ed463a7073 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-18T02:05:28Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-2e2fef0bac994271859537ed463a70732022-12-21T21:24:35ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-02-011510.3389/fnins.2021.620176620176Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic MiceYanmin Chang0Yi Yao1Rong Ma2Zemin Wang3Junjie Hu4Yanqing Wu5Xingjun Jiang6Lulu Li7Gang Li8Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHarvard Medical School, Boston, MA, United StatesDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaAlzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD.https://www.frontiersin.org/articles/10.3389/fnins.2021.620176/fullDl-3-n-butylphthalidetauP301Scognitive deficitsneuroinflammation |
| spellingShingle | Yanmin Chang Yi Yao Rong Ma Zemin Wang Junjie Hu Yanqing Wu Xingjun Jiang Lulu Li Gang Li Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice Frontiers in Neuroscience Dl-3-n-butylphthalide tau P301S cognitive deficits neuroinflammation |
| title | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
| title_full | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
| title_fullStr | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
| title_full_unstemmed | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
| title_short | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
| title_sort | dl 3 n butylphthalide reduces cognitive deficits and alleviates neuropathology in p301s tau transgenic mice |
| topic | Dl-3-n-butylphthalide tau P301S cognitive deficits neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.620176/full |
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