{"title":"Microarray-based Analysis of Differential Gene Expression Profile in Rotenone-induced Parkinson's Disease Zebrafish Model.","authors":"Yong Hui Nies, Mohamad Fairuz Yahaya, Wei Ling Lim, Seong Lin Teoh","doi":"10.2174/1871527322666230608122552","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & objectives: </strong>Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure.</p><p><strong>Methods: </strong>A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenonetreated (n = 19). Fish were treated with rotenone water (5 μg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR.</p><p><strong>Results: </strong>Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression (<i>dat, th1</i>, and <i>th2, p</i> < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes (<i>gzm3, cd8a, p</i> < 0.001) and T cell receptor signaling (<i>themis, lck, p </i>< 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation (<i>tyrobp, p</i> < 0.001), cellular response to IL-1 (<i>ccl34b4, il2rb, p</i> < 0.05), and regulation of apoptotic process (<i>dedd1, p</i> < 0.001) were also upregulated significantly.</p><p><strong>Conclusion: </strong>The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenonetreated zebrafish.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"761-772"},"PeriodicalIF":2.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS & neurological disorders drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1871527322666230608122552","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background & objectives: Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure.
Methods: A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenonetreated (n = 19). Fish were treated with rotenone water (5 μg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR.
Results: Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression (dat, th1, and th2, p < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes (gzm3, cd8a, p < 0.001) and T cell receptor signaling (themis, lck, p < 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation (tyrobp, p < 0.001), cellular response to IL-1 (ccl34b4, il2rb, p < 0.05), and regulation of apoptotic process (dedd1, p < 0.001) were also upregulated significantly.
Conclusion: The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenonetreated zebrafish.
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Aims & Scope
CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.
CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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