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Communication

Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish

by
Lakshmi Narasimha Murthy Chavali
1,
Ingeborg Yddal
1,
Ersilia Bifulco
1,
Simen Mannsåker
1,
Dagne Røise
1,
Jack O. Law
1,
Ann-Kristin Frøyset
1,
Sushma N. Grellscheid
1,2 and
Kari E. Fladmark
1,*
1
Department of Biological Sciences, University of Bergen, 5020 Bergen, Norway
2
Computational Biology Unit, University of Bergen, 5020 Bergen, Norway
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(7), 6456; https://doi.org/10.3390/ijms24076456
Submission received: 30 January 2023 / Revised: 22 March 2023 / Accepted: 27 March 2023 / Published: 29 March 2023
(This article belongs to the Section Biochemistry)
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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.
Keywords: Park7; DJ-1; zebrafish; Parkinson’s disease; behavior; NAD metabolism Park7; DJ-1; zebrafish; Parkinson’s disease; behavior; NAD metabolism

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MDPI and ACS Style

Chavali, L.N.M.; Yddal, I.; Bifulco, E.; Mannsåker, S.; Røise, D.; Law, J.O.; Frøyset, A.-K.; Grellscheid, S.N.; Fladmark, K.E. Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish. Int. J. Mol. Sci. 2023, 24, 6456. https://doi.org/10.3390/ijms24076456

AMA Style

Chavali LNM, Yddal I, Bifulco E, Mannsåker S, Røise D, Law JO, Frøyset A-K, Grellscheid SN, Fladmark KE. Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish. International Journal of Molecular Sciences. 2023; 24(7):6456. https://doi.org/10.3390/ijms24076456

Chicago/Turabian Style

Chavali, Lakshmi Narasimha Murthy, Ingeborg Yddal, Ersilia Bifulco, Simen Mannsåker, Dagne Røise, Jack O. Law, Ann-Kristin Frøyset, Sushma N. Grellscheid, and Kari E. Fladmark. 2023. "Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish" International Journal of Molecular Sciences 24, no. 7: 6456. https://doi.org/10.3390/ijms24076456

APA Style

Chavali, L. N. M., Yddal, I., Bifulco, E., Mannsåker, S., Røise, D., Law, J. O., Frøyset, A.-K., Grellscheid, S. N., & Fladmark, K. E. (2023). Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish. International Journal of Molecular Sciences, 24(7), 6456. https://doi.org/10.3390/ijms24076456

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