Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice
Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whe...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00437/full |
| _version_ | 1811234598494928896 |
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| author | Qing Zhang Yiyuan Xia Hongbin Luo Sheng Huang Yongjun Wang Yangping Shentu Yacoubou Abdoul Razak Mahaman Fang Huang Dan Ke Qun Wang Rong Liu Jian-Zhi Wang Jian-Zhi Wang Bin Zhang Xiaochuan Wang Xiaochuan Wang |
| author_facet | Qing Zhang Yiyuan Xia Hongbin Luo Sheng Huang Yongjun Wang Yangping Shentu Yacoubou Abdoul Razak Mahaman Fang Huang Dan Ke Qun Wang Rong Liu Jian-Zhi Wang Jian-Zhi Wang Bin Zhang Xiaochuan Wang Xiaochuan Wang |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases. |
| first_indexed | 2024-04-12T11:40:05Z |
| format | Article |
| id | doaj.art-ae0d9bd6b2d34b0da675b6a8070d53aa |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T11:40:05Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-ae0d9bd6b2d34b0da675b6a8070d53aa2022-12-22T03:34:43ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-11-011110.3389/fnmol.2018.00437412859Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected MiceQing Zhang0Yiyuan Xia1Hongbin Luo2Sheng Huang3Yongjun Wang4Yangping Shentu5Yacoubou Abdoul Razak Mahaman6Fang Huang7Dan Ke8Qun Wang9Rong Liu10Jian-Zhi Wang11Jian-Zhi Wang12Bin Zhang13Xiaochuan Wang14Xiaochuan Wang15Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaMedical College, Hubei University for Nationalities, Enshi, ChinaMedical College, Hubei University for Nationalities, Enshi, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaCodonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.https://www.frontiersin.org/article/10.3389/fnmol.2018.00437/fullAlzheimer’s diseaseCodonopsis pilosula polysaccharidePP2Ataucognitive impairment |
| spellingShingle | Qing Zhang Yiyuan Xia Hongbin Luo Sheng Huang Yongjun Wang Yangping Shentu Yacoubou Abdoul Razak Mahaman Fang Huang Dan Ke Qun Wang Rong Liu Jian-Zhi Wang Jian-Zhi Wang Bin Zhang Xiaochuan Wang Xiaochuan Wang Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice Frontiers in Molecular Neuroscience Alzheimer’s disease Codonopsis pilosula polysaccharide PP2A tau cognitive impairment |
| title | Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice |
| title_full | Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice |
| title_fullStr | Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice |
| title_full_unstemmed | Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice |
| title_short | Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice |
| title_sort | codonopsis pilosula polysaccharide attenuates tau hyperphosphorylation and cognitive impairments in htau infected mice |
| topic | Alzheimer’s disease Codonopsis pilosula polysaccharide PP2A tau cognitive impairment |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00437/full |
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