ZeEfficacy – Efficacy Services

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Parkinson Disease Model

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain. 

Exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces selective loss of zebrafish dopaminergic neurons also, eliciting symptoms characteristic of PD. This model allows identifying compounds that prevent the loss of dopaminergic neurons and the subsequent behavioral alterations.

Applications

  • Study dopaminergic neuronal population.
  • Study the molecular and physiological mechanisms of PD.
  • High throughput screening of new therapeutic compounds for PD.

Advantages

High conservation of zebrafish dopaminergic system with vertebrates and humans.

MPTP neurotoxicity in zebrafish larvae occous by the same mechanisms as in mammals, nevertheless thanks to the large progenies in zebrafish we can test a high number of compounds simultaneously.

Transparent embryos permit in vivo characterization of specific neuronal populations.

Automated locomotion monitoring rapidly highlights Parkinsonian phenotype rescue, identifying promising therapeutic compounds.

Method description

The assay consists of co-incubating the candidate drug together with the neurotoxin MPTP and evaluating the neurological activity and subsequent behavior on the treated larvae. Phenotypic parameters are characterized after a dark/light pattern phase. After the first locomotion evaluation, the most promising condition will be studied by diencephalic dopaminergic population assessment. This evaluation is focused on the tuberculum area by the in situ hybridization technique enabling visualization of dopaminergic neurons.

Readouts

  • Toxicity: determination of Lethal Concentration 50 (LC50), Benchmark Dose (BMD), and mortality.
  • Locomotion activity: total distance moved, symptomatic movement patterns, light/dark or tapping stimuli responses. Automated monitoring with DanioVision™ software (Noldus IT).
  • Dopaminergic neurons: quantification of dopaminergic neurons in the diencephalic region by anti-tyrosine hydroxylase (anti-TH) immunolabeling.
Figure 1. Locomotion activity evaluation. MPTP-treated larvae show a strong locomotion activity decrease, in comparison to control siblings.

References

  1. McKinley ET, Baranowski TC, Blavo DO, Cato C, Doan TN, Rubinstein AL. Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res Mol Brain Res. 2005 Nov 30;141(2):128-37.