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New research from scientists at Baylor College of Medicine shows that a combination of deep brain stimulation (DBS) and exercise has potential benefits for treating ataxia, a rare genetic neurodegenerative disease characterized by progressive irreversible movement problems.

Working with a mouse model of the human condition, researchers from Baylor and the Neurological Research Institute of Jan and Dan Duncan at Texas Children’s Hospital found that the combination of DBS versus the cerebellum, an important motor center in the brain, and movement caused coordination and quilting of the limbs and that the benefits persisted without further stimulation. In addition, the study reports that stimulation of mice with early-stage ataxia showed the most dramatic improvements. These and other findings, published in the journal Nature Communications, provide valuable new insights in developing future DBS strategies for treating the human condition.

“People with ataxia usually have progressive movement problems, including balance and coordination disorders that affect the person’s ability to walk, speak, and use fine motor skills. Treatments for this condition are limited, and patients typically survive 15 to 20 years after the symptoms appear first, “said lead author Lauren Miterko, a PhD student in Dr. Roy Sillitoe’s laboratory in Baylor.

DBS is currently used to relieve motor dysfunction in Parkinson’s disease and other movement conditions, but its value in treating ataxia has not been extensively studied. In this study, researchers worked with Car8, a mouse model of hereditary ataxia, to investigate whether adjusting the parameters of DBS and the stimulation target location would help increase the effectiveness of treatment for the disease.

Frequency is important

“We targeted the cerebellum first because it is a primary motor center in the brain and this target for DBS has had encouraging results in treating motor problems associated with other conditions such as stroke,” said Miterko. “We systematically targeted the cerebellum at different DBS frequencies and determined if there was an optimal frequency that would make the treatment more effective. When we used a specific frequency of 13 Hz, the motor skills in our Car8 mice improved. “

DBS plus exercise improved results

Neurostimulation with DBS improved muscle function and general mobility in Car8 mice, but researchers looked for additional ways to improve the condition.

“We know that exercise in general can benefit both muscle and neuronal health. Previous work on Parkinson’s and stroke patients mentioned that neuromodulation techniques combined with physical stimulation showed benefits. So we decided to incorporate exercise into ours Include investigation, “said Miterko. “We found that when the animals were given DBS while exercising on a treadmill, they showed improvements in motor coordination and pedaling that we had not seen with DBS alone.”

“In our ataxia model, the improvements did not disappear after a week of treatment, which has important practical implications for potential clinical applications,” said co-author Dr. Meike E. van der Heijden, postdoc in the Sillitoe laboratory. “In addition, all of the young mice responded with early-stage ataxia, suggesting that early treatment may continue to be of greatest benefit to patients in the future.”

Researchers also gained insight into the types of brain cells involved in restoring movement in this ataxia mouse model. They found that Purkinje cell neurotransmission is required for DBS to be effective. Purkinje cells are a type of neuron located in the cerebellar cortex of the brain. These cells are involved in regulating movement, balance and coordination, among other things.

“One of our goals is to further elucidate the role of Purkinje cells in recovery from ataxia,” said van der Heijden.

“We are particularly pleased with the results of this study, as it may be possible to extrapolate our approach to treating not only other motor disorders, but possibly also non-motor neuropsychiatric disorders,” said the author in question, Dr. Roy Sillitoe, Associate Professor of Pathology and Immunology and Neuroscience at Baylor College of Medicine and Director of the Neuropathology Core facility at Jan and Dan Duncan’s Neurological Research Institute at Texas Children’s Hospital.

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More information:
Lauren N. Miterko et al., Neuromodulation of the Cerebellum Rescues Movement in a Mouse Model of Ataxia, Nature Communications (2021). DOI: 10.1038 / s41467-021-21417-8 Provided by Baylor College of Medicine

Quote: Deep brain stimulation and movement restore movement in ataxia (2021, February 26), accessed February 27, 2021 from

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