PUBLICATION

Optimization of Zebrafish Larvae 6-OHDA Exposure for Neurotoxin Induced Dopaminergic Marker Reduction

Authors
Romero, A., Sanchez, A., Jones, J.D., Ledesma, K., El-Halawany, M.S., Hamouda, A.K., Bill, B.R.
ID
ZDB-PUB-240413-2
Date
2024
Source
Zebrafish   21(4): 287-293 (Journal)
Registered Authors
Bill, Brent
Keywords
6-OHDA, Parkinson's disease, RT-qPCR, superoxide dismutase, tyrosine hydroxylase, zebrafish
MeSH Terms
  • Disease Models, Animal
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Zebrafish*/genetics
  • Dopaminergic Neurons*/drug effects
  • Dopaminergic Neurons*/metabolism
  • Protein Serine-Threonine Kinases
  • Larva*/drug effects
  • Larva*/genetics
  • Larva*/growth & development
  • Superoxide Dismutase/genetics
  • Superoxide Dismutase/metabolism
  • Animals
  • Neurotoxins/toxicity
  • Oxidopamine*/pharmacology
PubMed
38608227 Full text @ Zebrafish
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder that is clinically assessed by motor symptoms associated with the loss of midbrain dopaminergic neurons affecting the quality of life for over 8.5 million people worldwide. The neurotoxin 6-hydroxydopamine (6-OHDA) has been used to chemically induce a PD-like state in zebrafish larvae by several laboratories; however, highly variable concentration, methodology, and reagents have resulted in conflicting results suggesting a need to investigate these issues of reproducibility. We propose a protocol that addresses the differences in methodology and induces changes in 6 days postfertilization (dpf) larvae utilizing a 24-h exposure at 3 dpf with 30 μM 6-OHDA. Despite ∼50% lethality, no morphological or development differences in surviving fish are observed. Definition of our model is defined by downregulation of the expression of th1 by reverse transcriptase-quantitative polymerase chain reaction, a marker for dopaminergic neurons and a reduction in movement. Additionally, we observed a downregulation of pink1 and an upregulation of sod1 and sod2, indicators of mitochondrial dysfunction and response to reactive oxygen species, respectively.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping