PUBLICATION
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated adult zebrafish as a model for Parkinson's Disease
- Authors
- Bagwell, E., Shin, M., Henkel, N., Migliaccio, D., Peng, C., Larsen, J.
- ID
- ZDB-PUB-240925-10
- Date
- 2024
- Source
- Neuroscience letters 842: 137991 (Journal)
- Registered Authors
- Keywords
- Animal Model, Disorders, MPTP, Movement, Neurodegeneration, Parkinsonism, Zebrafish
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*/pharmacology
- Parkinsonian Disorders/chemically induced
- Parkinsonian Disorders/metabolism
- Disease Models, Animal*
- Zebrafish*
- Dopamine Plasma Membrane Transport Proteins/genetics
- Dopamine Plasma Membrane Transport Proteins/metabolism
- Parkinson Disease/drug therapy
- Parkinson Disease/metabolism
- Male
- Animals
- PubMed
- 39317270 Full text @ Neurosci. Lett.
Citation
Bagwell, E., Shin, M., Henkel, N., Migliaccio, D., Peng, C., Larsen, J. (2024) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated adult zebrafish as a model for Parkinson's Disease. Neuroscience letters. 842:137991.
Abstract
Dopamine (DA) is a catecholamine neurotransmitter that works to regulate cognitive functions. Patients affected by Parkinson's Disease (PD) experience a loss of dopaminergic neurons and downregulated neural DA production. This leads to cognitive and physical decline that is the hallmark of PD for which no cure currently exists.. Danio rerio, or zebrafish, have become an increasingly popular disease model used in PD pharmaceutical development. This model still requires extensive development to better characterize which PD features are adequately represented. Furthermore, the great majority of PD zebrafish models have been performed in embryos, which may not be relevant towards age-related human PD. As an improvement, mature D. rerio were treated with neurotoxic prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through intraperitoneal injection to induce parkinsonism. Behavioral analysis confirmed disparities in movement between saline-injected control and the MPTP-injected experimental group, with swim distance and speed significantly lowered seven days after MPTP injection. Simultaneously, cognitive decline was apparent in MPTP-injected zebrafish, demonstrated by decreased alternation in a y-maze. RT-qPCR confirmed trends consistent with downregulation in Parkinsonian genetic markers, specifically DA transporter (DAT), MAO-B, PINK1. In summary, mature zebrafish injected with MPTP present with similar movement and cognitive decline as compared to human disease. Despite its benefits, this model does not appear to recapitulate full pathophysiology of the disease with the full profile of expected gene downregulation. Because of this, it is important that researchers looking for pharmacological interventions for PD only use this zebrafish model when targeting the human-relevant PD symptoms and causes that are represented.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping