New research from scientists at Baylor College of Medicine shows that a combination of deep brain stimulation (DBS) and exercise has potential benefits for the treatment of ataxia, a rare genetic neurodegenerative disease characterized by progressive, irreversible problems with movement.
Working with a mouse model of the human condition, researchers at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital found that the combination of DBS targeting the cerebellum, a major motor center in the brain, and the exercise saved the coordination of limbs and walking. and that the benefits continued without further stimulation. In addition, the study reports that stimulation of mice with ataxia at an early stage showed the most dramatic improvements. These and other results, published in the journal Nature communications, provide valuable new information in the design of future DBS strategies to treat the human condition.
“People with ataxia usually have progressive movement problems, including balance and coordination problems that affect a person’s ability to walk, speak and use fine motor skills. There are limited treatment options for this condition, and patients typically survive 15 to 20 years after symptoms. appear for the first time, ”said first author Lauren Miterko, a graduate student of Dr. Roy Sillitoe’s lab at Baylor.
DBS is currently used to relieve motor dysfunction in Parkinson’s disease and other movement conditions, but its value in the treatment of ataxia has not been widely explored. In this study, the researchers worked with Car8, a mouse model of inherited ataxia to determine whether adjusting DBS parameters and the location of the stimulation target would help increase the effectiveness of treatment for the disease.
“We first targeted the cerebellum because it is a primary motor center in the brain and this target location for DBS has seen encouraging success in treating motor problems associated with other conditions, such as stroke. “said Miterko. “We systematically targeted the cerebellum with different frequencies of DBS and determined if there was an optimal frequency that would increase the effectiveness of the treatment. When we used a particular frequency, 13 Hz, that’s when the function motor movement improved in our Car8 mice. ”
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, and previous work in Parkinson’s disease and stroke patients has mentioned that neuromodulation techniques combined with physical stimulation had benefits, so we decided to include exercise in our investigation, ”Miterko said. “We found that when animals received DBS during exercise on a treadmill, there were improvements in motor coordination and gait that we did not see with DBS alone.”
“In our model of ataxia, 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, Associate postdoctoral fellow at the Sillitoe laboratory. “Additionally, all of the young mice with early-stage ataxia responded, suggesting that it is possible that early treatment may also offer the greatest benefit to patients in the future.
The researchers also obtained information on the type of brain cells involved in the process of restoring movement in this mouse model of ataxia. They found that neurotransmission of Purkinje cells is necessary 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 the regulation of movement, balance and coordination among other functions.
“One of our goals is to better elucidate the role Purkinje cells play in recovery from ataxia,” said van der Heijden.
“We are particularly excited by the results of this study as it is possible to extrapolate our approach to treat not only other motor diseases, but possibly non-motor neuropsychiatric conditions as well,” said the corresponding author, the Dr Roy Sillitoe, Associate Professor of Pathology. and Immunology and Neuroscience at Baylor College of Medicine, and Director of the Center for Neuropathology at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.
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Lauren N. Miterko et al, Neuromodulation of the cerebellum saves movement in a mouse model of ataxia, Nature communications (2021). DOI: 10.1038 / s41467-021-21417-8
Quote: Deep Brain Stimulation and Exercise Restore Movement in Ataxia (2021, February 26) retrieved February 27, 2021 from https://medicalxpress.com/news/2021-02-deep-brain-movement-ataxia. html
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