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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 for identifying compounds that prevent the loss of dopaminergic neurons and the subsequent behavioral alterations.
High throughput in vivo efficacy screening based on complex behavioral endpoints.
High conservation of zebrafish dopaminergic system with vertebrates and humans.Mammal MPTP-induced neurotoxicity mechanism is conserved in zebrafish.Automated locomotion monitoring allows reproducibility testing and unbiased results.Behavioral endpoints, which entails complex connections, in an in vivo model with high experimental throughput.Transparent embryos permit in vivo characterization of specific neuronal populations.
High conservation of zebrafish dopaminergic system with vertebrates and humans.
Mammal MPTP-induced neurotoxicity mechanism is conserved in zebrafish.
Automated locomotion monitoring allows reproducibility testing and unbiased results.
Behavioral endpoints, which entails complex connections, in an in vivo model with high experimental throughput.
Transparent embryos permit in vivo characterization of specific neuronal populations.
The assay consists of co-incubating the candidate drug together with the neurotoxin MPTP and evaluating the locomotor behavior of the treated larvae. The experimental protocol for MPTP-induced Parkinson's phenotype consists of 25min dark/light alternating environments (5 min each). Optionally, the startling behavior in response to mechanical stimuli (tapping) and the diencephalic dopaminergic neuron population can be assessed in treated larvae. This evaluation is focused on the tuberculum area by the in situ hybridization technique enabling visualization of dopaminergic neurons.
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