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In experiments with mice, scientists were able to activate certain brain cells to ease movement symptoms similar to those of Parkinson’s disease (PD). The results may help explain the effects of deep brain stimulation (DBS) surgery on Parkinson’s symptoms, and may pave the way to developing longer-lasting therapies. The study appears in the May 8 online edition of Nature Neuroscience.
Parkinson’s develops when brain levels of dopamine drop. When dopamine levels are low, as they are in PD, nerve cells in an area of the brain called the globus pallidus misfire, affecting movement. Aryn H. Gittis, Ph.D., and colleagues at Carnegie Mellon University, wanted to understand how different types of brain cells in the globus pallidus affect movement. They conducted preliminary research with support from the Parkinson’s Foundation.
Dr. Gittis and coworkers used a cutting edge technique called optogenetics to study subtypes of brain cells in the external globus pallidus. They carried out their experiments in mice with PD-like symptoms and low levels of dopamine in the brain, which caused the animals to move slowly or not at all. Using optogenetics, they selectively activated different types of cells in the brain.
- Using a protocol similar to DBS, researchers found that broad stimulation of various brain cells of the globus pallidus restored the movement for mice. However, when the stimulation stopped, the mice stopped moving.
- When researchers used the target stimulation of one particular type of brain cell in the globus pallidus (PV cells) mice moved more easily. Repeated stimulation of this cell type led to less PD-like symptoms and faster movement.
- Researchers identified another brain cells as the “culprit" preventing PV cells from doing their job. They also found a way to inhibit or stop those cells, that led to improved movement in mice for hours after the stimulation stopped.
What Does It Mean?
Deep brain stimulation has been a major advance in controlling the symptoms of PD. Stimulation often targets one of two regions, the subthalamus and the globus pallidus. However, the exact mechanism leading to PD symptomatic relief with stimulation is unknown. Therefore, a better understanding of how the brain cells that control movement are affected in PD is important.
The significance of this study is that it shows that certain brain cells in the region called the globus pallidus — one of two brain regions where DBS electrodes are implanted — when selectively activated, ease PD symptoms and improve movement in animals. Importantly, stimulation of these brain cells leads to symptom relief that lasts for hours after the stimulation has stopped. Therefore, any medication developed to target these cells could possibly benefit people with PD with longer-lasting effects on movement than therapies available now.
Because these brain cells can be identified due to their unique molecular characteristics, it might be possible to target these cells — PV cells — with specific drugs that provide the benefit of DBS without the surgery. The results may also shed light on another potential new DBS technique, called coordinated reset. Read more about this technique, which is being studied with Parkinson's Foundation funding.
Reference: Mastro KJ, Zitelli KT, Willard AM, Leblanc KH, Kravitz A, Gittis AH. (2017). Cell-Specific Pallidal Intervention Induces Long-Lasting Motor Recovery in Dopamine-Depleted Mice. Nature Neuroscience doi:10.1038/nn.4559