Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish
DJ-1 is a redox sensitive protein with a wide range of functions related to oxidative stress protection. Mutations in the <i>park7</i> gene, which codes for DJ-1 are associated with early onset familial Parkinson’s disease and increased astrocytic DJ-1 levels are found in pathologic tiss...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6456 |
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| author | Lakshmi Narasimha Murthy Chavali Ingeborg Yddal Ersilia Bifulco Simen Mannsåker Dagne Røise Jack O. Law Ann-Kristin Frøyset Sushma N. Grellscheid Kari E. Fladmark |
| author_facet | Lakshmi Narasimha Murthy Chavali Ingeborg Yddal Ersilia Bifulco Simen Mannsåker Dagne Røise Jack O. Law Ann-Kristin Frøyset Sushma N. Grellscheid Kari E. Fladmark |
| author_sort | Lakshmi Narasimha Murthy Chavali |
| collection | DOAJ |
| description | DJ-1 is a redox sensitive protein with a wide range of functions related to oxidative stress protection. Mutations in the <i>park7</i> gene, which codes for DJ-1 are associated with early onset familial Parkinson’s disease and increased astrocytic DJ-1 levels are found in pathologic tissues from idiopathic Parkinson’s disease. We have previously established a DJ-1 knockout zebrafish line that developed normally, but with aging the DJ-1 null fish had a lowered level of tyrosine hydroxylase, respiratory mitochondrial failure and a lower body mass. Here we have examined the DJ-1 knockout from the early adult stage and show that loss of DJ-1 results in a progressive, age-dependent increase in both motoric and non-motoric symptoms associated to Parkinson’s disease. These changes coincide with changes in mitochondrial and mitochondrial associated proteins. Recent studies have suggested that a decline in NAD+ can contribute to Parkinson’s disease and that supplementation of NAD+ precursors may delay disease progression. We found that the brain NAD+/NADH ratio decreased in aging zebrafish but did not correlate with DJ-1 induced altered behavior. Differences were first observed at the late adult stage in which NAD+ and NADPH levels were decreased in DJ-1 knockouts. Considering the experimental power of zebrafish and the development of Parkinson’s disease-related symptoms in the DJ-1 null fish, this model can serve as a useful tool both to understand the progression of the disease and the effect of suggested treatments. |
| first_indexed | 2024-03-11T05:34:39Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:39Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2f6af4fcf06841378c893b816c97c16c2023-11-17T16:51:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247645610.3390/ijms24076456Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout ZebrafishLakshmi Narasimha Murthy Chavali0Ingeborg Yddal1Ersilia Bifulco2Simen Mannsåker3Dagne Røise4Jack O. Law5Ann-Kristin Frøyset6Sushma N. Grellscheid7Kari E. Fladmark8Department of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDepartment of Biological Sciences, University of Bergen, 5020 Bergen, NorwayDJ-1 is a redox sensitive protein with a wide range of functions related to oxidative stress protection. Mutations in the <i>park7</i> gene, which codes for DJ-1 are associated with early onset familial Parkinson’s disease and increased astrocytic DJ-1 levels are found in pathologic tissues from idiopathic Parkinson’s disease. We have previously established a DJ-1 knockout zebrafish line that developed normally, but with aging the DJ-1 null fish had a lowered level of tyrosine hydroxylase, respiratory mitochondrial failure and a lower body mass. Here we have examined the DJ-1 knockout from the early adult stage and show that loss of DJ-1 results in a progressive, age-dependent increase in both motoric and non-motoric symptoms associated to Parkinson’s disease. These changes coincide with changes in mitochondrial and mitochondrial associated proteins. Recent studies have suggested that a decline in NAD+ can contribute to Parkinson’s disease and that supplementation of NAD+ precursors may delay disease progression. We found that the brain NAD+/NADH ratio decreased in aging zebrafish but did not correlate with DJ-1 induced altered behavior. Differences were first observed at the late adult stage in which NAD+ and NADPH levels were decreased in DJ-1 knockouts. Considering the experimental power of zebrafish and the development of Parkinson’s disease-related symptoms in the DJ-1 null fish, this model can serve as a useful tool both to understand the progression of the disease and the effect of suggested treatments.https://www.mdpi.com/1422-0067/24/7/6456<i>Park7</i>DJ-1zebrafishParkinson’s diseasebehaviorNAD metabolism |
| spellingShingle | Lakshmi Narasimha Murthy Chavali Ingeborg Yddal Ersilia Bifulco Simen Mannsåker Dagne Røise Jack O. Law Ann-Kristin Frøyset Sushma N. Grellscheid Kari E. Fladmark Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish International Journal of Molecular Sciences <i>Park7</i> DJ-1 zebrafish Parkinson’s disease behavior NAD metabolism |
| title | Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish |
| title_full | Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish |
| title_fullStr | Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish |
| title_full_unstemmed | Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish |
| title_short | Progressive Motor and Non-Motor Symptoms in <em>Park7</em> Knockout Zebrafish |
| title_sort | progressive motor and non motor symptoms in em park7 em knockout zebrafish |
| topic | <i>Park7</i> DJ-1 zebrafish Parkinson’s disease behavior NAD metabolism |
| url | https://www.mdpi.com/1422-0067/24/7/6456 |
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