- Zebrafish Germ Cell Tumor Models
- Zebrafish Intestinal Cancer Models
- Zebrafish Intrahepatic Cholangiocarcinoma Models
- Zebrafish Liver Cancer Models
- Zebrafish Melanoma Models
- Zebrafish Neurofibromatosis Type 1 Models
- Zebrafish Pancreatic Cancer Models
- Zebrafish Retinoblastoma Models
- Zebrafish Rhabdomyosarcoma Models
- Zebrafish Thyroid Cancer Models
Zebrafish Parkinson's Disease Models
Parkinson's disease (PD) is one of the most common neurodegenerative diseases affecting the motor system and includes major motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to increased longevity. However, there is currently no adequate cure for this disease in terms of treatment strategies and symptom control. One of the main challenges facing researchers is having a suitable research model.
Rodents are the most commonly used PD models, but no single model can replicate the true nature of PD. Despite clear differences between fish and mammals, zebrafish share genomic and physiological homology with humans. The zebrafish brain has all the major structures found in the mammalian brain, has a neurotransmitter system, and also has a functional blood-brain barrier similar to that of humans. From the perspective of PD research, zebrafish possess a ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. Furthermore, zebrafish appears to be a viable model to study PD due to its aminergic structure, MPTP mode of action, and PINK1 action similar to those of mammals.
Fig. 3 Parkinson's disease molecular mechanisms and effects in the zebrafish central nervous system induced by several Parkinson's disease agents and treatment alternatives.
Our Zebrafish Parkinson's Disease Models
Creative Biogene has established a variety of zebrafish models that can be used to study PD, namely chemically induced models and genetic models. Among these models, chemical and genetic zebrafish models of PD can reproduce several biochemical, neurochemical, morphological, and neurobehavioral features of the human disease. Importantly, the pharmacological responses of these models to drugs used in the clinic are also conserved. In addition, zebrafish gene orthologs of PD-related human genes are particularly conserved in sequence and function, as well as the roles of the respective proteins in cellular pathways. Taken together, these zebrafish models can complement the use of other animal models for PD mechanism studies and facilitate the screening of new potential therapeutic compounds.
Table 1. Chemically induced model of zebrafish Parkinson's disease models
| Zebrafish model | Pathological hallmarks | Motor phenotype |
|---|---|---|
| 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine | Decrease of dopamine levels Loss of dopaminergic neurons | Deficits in evoked swimming response (bradykinesia) Decrease in total distance moved and swimming velocity (bradykinesia) Increase in number and duration of freezing episodes (dyskinesia) |
| 6-Hydroxydopamine | Decrease of dopamine levels Loss of dopaminergic neurons | Decrease in total distance moved and swimming velocity (bradykinesia) |
| Paraquat | Decrease of dopamine levels | Decrease in total distance moved (bradykinesia) |
| Rotenone | Decrease of dopamine levels | Decrease in time swimming at high velocity (bradykinesia) |
| Cytotoxic metabolite of metronidazole | Decrease of dopamine levels Loss of dopaminergic neurons | Decrease in total distance moved and swimming velocity (bradykinesia) Increase in resting time and decrease in active time |
| Titanium dioxide nanoparticles | Loss of dopaminergic neurons | Decrease in total distance moved (bradykinesia) |
| Ziram | Loss of dopaminergic neurons | Decrease in total distance moved (bradykinesia) |
Table 2. Genetic zebrafish Parkinson's disease models.
| Zebrafish model | Pathological hallmarks | Motor phenotype |
|---|---|---|
| β- or γ1-Synucleins knockdown | Decrease of dopamine levels Delayed development of dopaminergic neurons | Decrease in swimming velocity (bradykinesia) |
| γ1-Synuclein overexpression | Synuclein aggregates | ND |
| Human α-synuclein overexpression | Synuclein aggregates | ND |
| Pinkl knockdown | Loss of dopaminergic neurons | Deficits in evoked swimming response (bradykinesia) Decrease in total distance moved (bradykinesia) |
| Parkin knockdown | Loss of dopaminergic neurons | No changes in total distance moved |
| DJ-1 knockdown | No loss of dopaminergic neurons | ND |
| ΔWD40-LRRK2 | Loss of dopaminergic neurons | Decrease in total distance moved (bradykinesia) |
| LRRK2 knockdown | Synuclein aggregates Loss of dopaminergic neurons | ND |
| FBXO7 knockdown | Loss of dopaminergic neurons | Decrease in swimming velocity (bradykinesia) |
| ATP13A2 knockdown | ND | Decrease in swimming velocity (bradykinesia) |
Advantages
- Real-time neuroimaging in zebrafish
- Gene functional analysis at specific time points
- High-throughput gene/drug screening
- Simple and efficient manipulation of multiple genes at physiologically relevant levels
References
- Najib NHM, et al. Modeling Parkinson's Disease in Zebrafish. CNS Neurol Disord Drug Targets. 2020, 19(5):386-399.
- Vaz RL, et al. Zebrafish as an Animal Model for Drug Discovery in Parkinson's Disease and Other Movement Disorders: A Systematic Review. Front Neurol. 2018, 9:347.
- Robea MA, et al. Parkinson's Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes. Oxid Med Cell Longev. 2020, 2020:1370837.
For research use only. Not intended for any clinical use.
