4.5 Article

Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson's Disease Models

Journal

BRAIN SCIENCES
Volume 12, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/brainsci12020268

Keywords

zonisamide; microglia; inflammation; mitochondria; Parkinson's disease

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan

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This study demonstrates the potential ameliorative effects of zonisamide on microglial mitochondrial dysfunction in Parkinson's disease, providing novel evidence for its clinical use as an antiparkinsonian drug.
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 mu g/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.

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