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 has emerged as a powerful 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:
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).
Genetic Pathways (RNASeq)
A chemical approach will be taken to induce Parkinson’s phenotypes. Compound screening can also use genetic models.
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:
The DanioVision software tracks the behavior of individual zebrafish larvae over time as they explore an arena.
PQT-induced Parkinson’s zebrafish model tested for Luciole Pharmaceuticals.
Compound X Rescues PQT-induced loss of movement. PQT-treated larvae show a strong decrease in locomotion as measured by distance moved during dark stimulation (pink line). In this example, treatment with the test compound induces a recovery of movement (green line) that is comparable to the control phenotype of untreated animals (black line).
Other Disease Modeling
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