Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models
Mitochondrial dysfunction and exacerbated neuroinflammation are critical factors in the pathogenesis of both familial and non-familial forms of Parkinson’s disease (PD). This study aims to understand the possible ameliorative effects of zonisamide on microglial mitochondrial dysfunction in PD. We pr...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/12/2/268 |
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| author | Satoshi Tada Mohammed E. Choudhury Madoka Kubo Rina Ando Junya Tanaka Masahiro Nagai |
| author_facet | Satoshi Tada Mohammed E. Choudhury Madoka Kubo Rina Ando Junya Tanaka Masahiro Nagai |
| author_sort | Satoshi Tada |
| collection | DOAJ |
| description | Mitochondrial dysfunction and exacerbated neuroinflammation are critical factors in the pathogenesis of both familial and non-familial forms of Parkinson’s disease (PD). This study aims to understand the possible ameliorative effects of zonisamide on microglial mitochondrial dysfunction in PD. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and lipopolysaccharide (LPS) co-treated mouse models of PD to investigate the effects of zonisamide on mitochondrial reactive oxygen species generation in microglial cells. Consequently, we utilised a mouse BV2 cell line that is commonly used for microglial studies to determine whether zonisamide could ameliorate LPS-treated mitochondrial dysfunction in microglia. Flow cytometry assay indicated that zonisamide abolished microglial reactive oxygen species (ROS) generation in PD models. Extracellular flux assays showed that LPS exposure to BV2 cells at 1 μg/mL drastically reduced the mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Zonisamide overcame the inhibitory effects of LPS on mitochondrial OCR. Our present data provide novel evidence on the ameliorative effect of zonisamide against microglial mitochondrial dysfunction and support its clinical use as an antiparkinsonian drug. |
| first_indexed | 2024-03-09T22:27:07Z |
| format | Article |
| id | doaj.art-88fef714f3b243e9afedac67ec525dfb |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T22:27:07Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-88fef714f3b243e9afedac67ec525dfb2023-11-23T19:04:13ZengMDPI AGBrain Sciences2076-34252022-02-0112226810.3390/brainsci12020268Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease ModelsSatoshi Tada0Mohammed E. Choudhury1Madoka Kubo2Rina Ando3Junya Tanaka4Masahiro Nagai5Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Toon 791-0295, Ehime, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, JapanDepartment of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Toon 791-0295, Ehime, JapanDepartment of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Toon 791-0295, Ehime, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, JapanDepartment of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Toon 791-0295, Ehime, JapanMitochondrial dysfunction and exacerbated neuroinflammation are critical factors in the pathogenesis of both familial and non-familial forms of Parkinson’s disease (PD). This study aims to understand the possible ameliorative effects of zonisamide on microglial mitochondrial dysfunction in PD. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and lipopolysaccharide (LPS) co-treated mouse models of PD to investigate the effects of zonisamide on mitochondrial reactive oxygen species generation in microglial cells. Consequently, we utilised a mouse BV2 cell line that is commonly used for microglial studies to determine whether zonisamide could ameliorate LPS-treated mitochondrial dysfunction in microglia. Flow cytometry assay indicated that zonisamide abolished microglial reactive oxygen species (ROS) generation in PD models. Extracellular flux assays showed that LPS exposure to BV2 cells at 1 μg/mL drastically reduced the mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Zonisamide overcame the inhibitory effects of LPS on mitochondrial OCR. Our present data provide novel evidence on the ameliorative effect of zonisamide against microglial mitochondrial dysfunction and support its clinical use as an antiparkinsonian drug.https://www.mdpi.com/2076-3425/12/2/268zonisamidemicrogliainflammationmitochondriaParkinson’s disease |
| spellingShingle | Satoshi Tada Mohammed E. Choudhury Madoka Kubo Rina Ando Junya Tanaka Masahiro Nagai Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models Brain Sciences zonisamide microglia inflammation mitochondria Parkinson’s disease |
| title | Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models |
| title_full | Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models |
| title_fullStr | Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models |
| title_full_unstemmed | Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models |
| title_short | Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models |
| title_sort | zonisamide ameliorates microglial mitochondriopathy in parkinson s disease models |
| topic | zonisamide microglia inflammation mitochondria Parkinson’s disease |
| url | https://www.mdpi.com/2076-3425/12/2/268 |
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