Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra
Objective: Levodopa (L-DOPA) is the primary treatment for Parkinson’s disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to probe the action of L-DOPA on NLR pyrin domain containing 3 (NLRP3) inflammasome activation and tyrosine hydroxylase (T...
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| Format: | Article |
| Language: | English |
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IMR Press
2024-01-01
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| Series: | Journal of Integrative Neuroscience |
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| Online Access: | https://www.imrpress.com/journal/JIN/23/1/10.31083/j.jin2301002 |
| _version_ | 1797338832877649920 |
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| author | Xi Chen Zhao Wang Weihua Yang Yuejun Fu |
| author_facet | Xi Chen Zhao Wang Weihua Yang Yuejun Fu |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | Objective: Levodopa (L-DOPA) is the primary treatment for Parkinson’s disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to probe the action of L-DOPA on NLR pyrin domain containing 3 (NLRP3) inflammasome activation and tyrosine hydroxylase (TH) levels in the striatum (STR) and substantia nigra (SN) of mice with PD symptoms. Methods: PD was simulated by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 25 mg/kg/d) to induce mice, followed by L-DOPA (8 mg/kg/d) treatment. The behavioral performance of the mice was assessed using the pole test, balance beam, and rotarod test. After euthanasia with 120 mg/kg sodium pentobarbital, STR and SN were collected for evaluation of protein level of TH, NLR pyrin domain containing 3 (NLRP3), ASC and Cleaved caspase-1 using Western blot and mRNA levels of TH, inflammatory factors IL-1β and IL-18 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Treatment with L-DOPA significantly ameliorated the behavioral deficits caused by MPTP in mice with PD symptoms. L-DOPA administration resulted in reduced levels of apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC), NLRP3, and Cleaved caspase-1 protein levels, and decreased mRNA levels of IL-1β and IL-18 in the STR and SN. L-DOPA increased the TH mRNA and TH protein levels, while suppressing NLRP3 inflammasome activation in the STR and SN of mice with PD symptoms. Conclusions: L-DOPA improves the behavioral deficits in mice with PD symptoms possibly by suppressing NLRP3 inflammasome activation and increasing TH levels in the STR and SN TH levels. These findings provide further perceptions into the property of L-DOPA in PD. |
| first_indexed | 2024-03-08T09:37:04Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-03-08T09:37:04Z |
| publishDate | 2024-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-a0aab3f74731485cb7024d779cb0967c2024-01-30T07:44:42ZengIMR PressJournal of Integrative Neuroscience0219-63522024-01-01231210.31083/j.jin2301002S0219-6352(23)00589-2Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia NigraXi Chen0Zhao Wang1Weihua Yang2Yuejun Fu3Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, 237016 Taiyuan, Shanxi, ChinaChangxing Pharmaceutical Co., Ltd., 313100 Huzhou, Zhejiang, ChinaChangxing Pharmaceutical Co., Ltd., 313100 Huzhou, Zhejiang, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, 237016 Taiyuan, Shanxi, ChinaObjective: Levodopa (L-DOPA) is the primary treatment for Parkinson’s disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to probe the action of L-DOPA on NLR pyrin domain containing 3 (NLRP3) inflammasome activation and tyrosine hydroxylase (TH) levels in the striatum (STR) and substantia nigra (SN) of mice with PD symptoms. Methods: PD was simulated by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 25 mg/kg/d) to induce mice, followed by L-DOPA (8 mg/kg/d) treatment. The behavioral performance of the mice was assessed using the pole test, balance beam, and rotarod test. After euthanasia with 120 mg/kg sodium pentobarbital, STR and SN were collected for evaluation of protein level of TH, NLR pyrin domain containing 3 (NLRP3), ASC and Cleaved caspase-1 using Western blot and mRNA levels of TH, inflammatory factors IL-1β and IL-18 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Treatment with L-DOPA significantly ameliorated the behavioral deficits caused by MPTP in mice with PD symptoms. L-DOPA administration resulted in reduced levels of apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC), NLRP3, and Cleaved caspase-1 protein levels, and decreased mRNA levels of IL-1β and IL-18 in the STR and SN. L-DOPA increased the TH mRNA and TH protein levels, while suppressing NLRP3 inflammasome activation in the STR and SN of mice with PD symptoms. Conclusions: L-DOPA improves the behavioral deficits in mice with PD symptoms possibly by suppressing NLRP3 inflammasome activation and increasing TH levels in the STR and SN TH levels. These findings provide further perceptions into the property of L-DOPA in PD.https://www.imrpress.com/journal/JIN/23/1/10.31083/j.jin2301002parkinson's diseaselevodopasubstantia nigrastriatumnlrp3tyrosine hydroxylase |
| spellingShingle | Xi Chen Zhao Wang Weihua Yang Yuejun Fu Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra Journal of Integrative Neuroscience parkinson's disease levodopa substantia nigra striatum nlrp3 tyrosine hydroxylase |
| title | Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra |
| title_full | Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra |
| title_fullStr | Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra |
| title_full_unstemmed | Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra |
| title_short | Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra |
| title_sort | levodopa improves behavioral deficits of mice with parkinson s disease symptoms via curbing nlrp3 inflammasome activation and enhancing tyrosine hydroxylase levels in the striatum and substantia nigra |
| topic | parkinson's disease levodopa substantia nigra striatum nlrp3 tyrosine hydroxylase |
| url | https://www.imrpress.com/journal/JIN/23/1/10.31083/j.jin2301002 |
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