Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish
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Published:2023-03-29
Issue:7
Volume:24
Page:6456
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Chavali Lakshmi1,
Yddal Ingeborg1,
Bifulco Ersilia1,
Mannsåker Simen1,
Røise Dagne1,
Law Jack1ORCID,
Frøyset Ann-Kristin1,
Grellscheid Sushma12,
Fladmark Kari1
Affiliation:
1. Department of Biological Sciences, University of Bergen, 5020 Bergen, Norway
2. Computational Biology Unit, University of Bergen, 5020 Bergen, Norway
Abstract
DJ-1 is a redox sensitive protein with a wide range of functions related to oxidative stress protection. Mutations in the park7 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.
Funder
Advokat Rolf Sandberg Rebergs
Ellen Marie Rebergs legat
Norges Parkinson Forskningsfond
Gerda Meyer Nyquist Guldbrandson
Gerdt Meyer Nyquists legat
Trond Mohn Stiftelse
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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