by A new study published in Nature Methods by researchers from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences has developed a breakthrough organoid model of the dopaminergic system. This model provides a deeper understanding of the functionality and connectivity of this system and its potential implications for Parkinson’s disease.
The dopaminergic system plays a crucial role in mediating the feeling of reward and fine motor control. However, key features of this system are still not fully understood, and there is currently no cure for Parkinson’s disease, a condition characterized by the loss of dopaminergic neurons and the subsequent loss of motor control.
The researchers at IMBA developed an organoid model of the dopaminergic system that accurately replicates its morphology, nerve projections, and functionality. Organoids are three-dimensional structures derived from human stem cells that can mimic the development and function of various human organs.
The team first developed organoid models of the ventral midbrain, striatum, and cortex, which are regions connected by dopaminergic neurons. They then fused these organoids together to mimic the wiring of dopaminergic neurons in the human brain, specifically the projections to the striatum and cortex.
Surprisingly, the researchers observed a high level of dopaminergic innervation and synapses forming between dopaminergic neurons and neurons in the striatum and cortex. To confirm the functionality of these neurons and synapses, the team collaborated with researchers from SAHMRI and Flinders University in Australia. When the midbrain, which contains dopaminergic neurons, was stimulated, the neurons in the striatum and cortex responded to the stimulation. This demonstrated that the organoid model accurately replicated the functionality of the dopaminergic circuit.
The development of this organoid model of the dopaminergic system holds great potential for improving cell therapies for Parkinson’s disease. Previous clinical studies have involved injecting precursor cells of dopaminergic neurons into the striatum to compensate for the loss of natural innervation. However, these studies have had mixed results.
The researchers conducted further studies using the organoid model and demonstrated that dopaminergic progenitor cells injected into the model matured into neurons and extended neuronal projections, similar to what occurs in the human brain. This suggests that the organoid system could be utilized as a platform for testing conditions for cell therapies, allowing researchers to observe how precursor cells behave in a three-dimensional human environment and how to differentiate them more efficiently.
In addition, the researchers investigated the effects of chronic cocaine exposure on the dopaminergic circuit using the organoid model. They exposed the organoids to cocaine over 80 days and found that it led to functional, morphological, and transcriptional changes in the dopaminergic circuit.
The most remarkable finding was that these changes persisted even after 25 days of withdrawal from cocaine exposure. This suggests that the long-term effects of dopaminergic overstimulation can be investigated using the organoid model.
Overall, the development of this organoid model sheds light on the secrets of the brain’s dopaminergic system and its role in Parkinson’s disease. It offers great promise for improving cell therapies and understanding the long-term effects of dopaminergic overstimulation in addiction. Further research and advancements in this field could pave the way for potential treatments and preventions for Parkinson’s disease and other dopaminergic-related disorders.
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1. Source: Coherent Market Insights, Public sources, Desk research
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