Tuesday April 8 2008
Parkinson's is caused by a loss of dopamine producing nerve cells (red) in the brain
“Parkinson’s trigger identified by scientists,” reports The Daily Telegraph today. It reveals that the brain cells responsible for triggering Parkinson’s disease have been identified and that this could lead to new ways to treat the condition. The newspaper goes on to say that the ’mother cells’ that produce and use dopamine (the lack of which leads to the symptoms of Parkinson’s) have been discovered in a study in mice. It adds that the researchers hope that the new understanding of how these neurones are produced can be used to develop novel therapies.
This animal study has shed light on some early processes of brain development in mouse embryos. However, at this early stage, it is unclear how relevant the findings are to development of the condition in the human brain, or how the findings apply to treatments for Parkinson’s disease.
Where did the story come from?
The research was carried out by Dr Sonia Bonilla and colleagues from the Karolinska Institutet in Stockholm, Sweden; the Max Planck Institute for Cell Biology and Genetics, Dresden, Germany; and the GSF-National Research Centre for Environmental and Health, Munich, Germany. The study was published in Glia, a peer-reviewed medical journal.
What kind of scientific study was this?
The chronic symptoms of Parkinson’s disease include movement disorders such as tremors, slow movement and stiffness. It is thought that these symptoms are caused by dwindling levels of a neurotransmitter called dopamine. Neurotransmitters are chemicals that are involved in the interaction between nerve cells (neurones) and other cells. Dopamine has several functions in the brain, including motor activity (voluntary movement) and is produced by dopaminergic neurones, the loss of which are associated with Parkinson's disease.
In this laboratory study in mice, the researchers were interested in exploring the relationship between neurones in a part of the developing brain called the ’floor plate’ in the midbrain, and dopaminergic neurones. Cells called ’radial glia-like cells’ are thought to act as scaffolds to allow dopaminergic neurones to migrate in the developing brain, providing support and nutrition for the cells. There is some debate in the literature as to exactly where in the brain the ancestors of dopaminergic neurones are, i.e. where in the developing mammal brain dopaminergic neurones first appear. In this study, the researchers were interested in exploring whether these radial glia-like cells also have a role to play in creating the dopaminergic neurones in the first place.
The researchers injected pregnant mice with a genetic marker (something that would show up in the DNA of cells). As the embryos of the mice developed, the marker would indicate the activity of developing cells as they grew and differentiated into various types of nerve cells, including dopaminergic neurones.
The experiments were complex, but in short they involved identifying regions of neural growth and specialisation in developing embryos. Further studies involved growing radial glia-like cells in a dish to see whether and how they would specialise.
What were the results of the study?
The researchers found that dopaminergic neurones appeared in the developing mouse embryos from day 10. They appeared for the first time in the floor plate of the front midbrain (the ventral mesencephalon brain region).
The researchers found that radial glia-like cells had neurogenic potential, i.e. they were able to make dopaminergic neurones. When they grew these radial glia-like cells in dishes, they found that, after five days, three per cent of their culture had specialised into dopaminergic neurones.
What interpretations did the researchers draw from these results?
The researchers conclude that their results support other literature and confirm that radial glia-like cells in the floor plate of the midbrain do more than just organise and guide migrating neurones; they can undergo ‘neurogenesis’, generating dopaminergic neurones in the midbrain region.
What does the NHS Knowledge Service make of this study?
This laboratory study will interest members of the scientific community. As the researchers describe, it adds to a growing body of evidence that these radial glia-like cells perform more functions than was originally thought. This study has found that, in the developing mouse embryo, they play a crucial role in the development of dopaminergic neurones.
The development of mouse models for human disease are important preliminary steps that can provide the basis for future experiments looking at the effectiveness of new treatments. However, at this very early stage, it is difficult to see how these findings can quickly translate into treatments for people with Parkinson’s. Studies in mice are rarely directly applicable to humans because of their different make up. Even these findings, which describe what is happening at a cellular level during embryonic development, will need to be replicated in human cells.
The more that is understood about the development of the brain and Parkinson’s, the closer that novel treatments for the condition will be. However, any treatment based on these new findings about radial glia-like cells is some time away.