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Parkinson's Disease

Parkinson’s disease is a neurodegenerative disorder that affects the movement of a person. It is caused by the degeneration and death of dopamine-producing neurons in a part of the brain called the substantia nigra. Parkinson’s disease is a chronic and progressive condition, and currently uncurable. There are treatments available that can help manage symptoms and improve quality of life.

Zebrafish As A Parkinson's Model

Zebrafish have become a popular animal model for Parkinson’s disease research. This is because they share many similarities with humans, including a similar nervous system and genetic makeup. Zebrafish are often used in Parkinson’s research in the following ways:
  • Modeling Parkinson’s disease using genetically modified or chemically-treated zebrafish mutants to study the mechanisms underlying Parkinson’s disease and to test potential treatments.
  • Identifying potential therapies through drug or compound screening. 
  • Understanding the genetics of Parkinson’s to study the function of Parkinson’s disease genes and identifing new genes that may be involved in the disease.

 

Our Approach

Because zebrafish are transparent during the early stages of development, researchers can easily observe the effects of the compounds on the fish’s neurons.

Larval zebrafish can be a particularly beneficial model of PD phenotypes because the developing zebrafish nervous system has been extensively studied, and is homologous to many aspects of the human nervous system. The similarities within the human and zebrafish dopaminergic system are especially useful. The zebrafish ventral telencephalon is considered homologous to the mammalian striatum (Stewart et al., 2014), a brain region that plays a critical role in motor and cognitive behaviors, and is connected to the substantia nigra via dopaminergic projections (Redgrave et al., 2010).

Disease Models Creation

Compound Screening

Behavior Assessment/Phenotype measurements

Our Offerings

Compound testing using a chemical model or genetically modified zebrafish model.

  • For a chemical model, we can expose zebrafish larvae to a chemical that induces a disease-like state and measure phenotypic behavior.
  • For a genetically modified model, we can edit the client’s gene of interest to model a specific disease, then measure phenotypic behavior.

Models

Behavior Analysis

Compound Screening

Genetic Pathways (RNASeq)

Genetic Model

Chemical Model

Our Services

1. Genetically modified zebrafish mutants for modeling Parkinson’s disease.

2. Compound screening & behavior assessment.
A chemical approach will be taken to induce Parkinson’s phenotypes. Compound screening can also use genetic models.

Behavior assessments

Age-matched animals from at least two different groups are compared. The animals are recorded in response to stimuli such as light/dark cycling and vibration. The software identifies and tracks animals to quantify many aspects of behavior, including:

  • Velocity 
  • Light/dark locomotor response
  • Vibrational startle response
  • Total distance moved

 

What data do we provide?

  • Locomotory activity: since Parkinson’s is primarily a movement disorder, we provide an overall readout of locomotion.
  • Thigmotaxis measurements: a readout of anxiety (a common symptom in Parkinson’s patients).
  • Whole mount brain imaging of dopaminergic neurons.

The DanioVision software tracks the behavior of individual zebrafish larvae over time as they explore an arena.

Light/dark larvae locomotion per minute. MPTP-treated larvae show a strong decrease in locomotion during dark and light phases. In this example, the test compound induces a partial recovery of the control phenotype, increasing larval locomotion during the dark phase. Means and SD are plotted.

Our Method for compounding testing and behavior assessment

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