Movement of ataxic patients can be restored by brain stimulation and exercise

A recent study from Baylor College of Medicine found that the combination of exercise and deep brain stimulation (DBS) was used to treat a rare hereditary neurodegenerative disease called ataxia, which is characterized by an irreversible problem of progressive exercise. It suggests that it may be useful.

Researchers at Baylor University and the Yandunkan Institute of Neurology at Texas Children’s Hospital used a mouse model of the human state to combine DBS for the cerebellum, the major motor center of the brain, to coordinate limbs. Discovered to rescue the footsteps. And the profits lasted without any further stimulation.

In addition, the study reports that stimulating mice with early-stage ataxia showed the most dramatic improvement. These and other findings, published in Nature Communications, provide valuable new insights in designing future DBS strategies for treating human conditions.

“People with ataxia usually have progressive problems with exercise, such as impaired balance and coordination, which affect walking, conversation, and use of fine motor skills. Treatment options for this condition are limited. , Patients usually survive 15 to 20 years after the onset of symptoms. First appearance. ” Lauren Mitelco, the lead author and graduate student in Dr. Roy Sillitoe’s lab in Baylor.

DBS is currently used to relieve Parkinson’s disease and other motor dysfunctions, but its value in the treatment of ataxia has not been extensively investigated. In this study, can researchers work with Car8, a mouse model of hereditary ataxia, to adjust DBS parameters and the location of stimulation targets to increase the effectiveness of treatment for that condition? I investigated whether it was.

Frequency is important

“The cerebellum is the primary motor cortex of the brain, and this target location in DBS first targets the cerebellum because it has been promising for treating motor problems related to other conditions such as stroke. We did, “said Miterko. “We systematically targeted the cerebellum at various frequencies in DBS to determine if there was an optimal frequency that would enhance the effectiveness of the treatment. When using a specific frequency of 13 Hz, the motor function of Car8 mice Has improved. “

DBS Plus exercise improved results

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

“In general, exercise has been shown to help both muscle and neuronal health. Previous studies of patients with Parkinson’s disease and stroke have stated that neuromodulatory techniques combined with physical stimulation are beneficial. We decided to include the movement in our investigation, “said Mitelco. .. “When animals received DBS while exercising on a treadmill, they saw improvements in motor coordination and stepping that were not observed with DBS alone.”

“Our model of ataxia did not improve after a week of treatment, which has important practical implications for potential clinical applications,” said a postdoc at the Sillitoe lab. Dr. Meike E. van der Heijden said. “It also suggests that all young mice with early-stage ataxia respond and early treatment may also have the greatest benefit to patients in the future.”

Researchers also gained insight into the types of brain cells involved in the process of restoring movement in this ataxic mouse model. They found that Purkinje cell neurotransmission was required for DBS to be effective. Purkinje cells are a type of neuron in the cerebellar cortex of the brain. These cells are involved in the regulation of movement, balance and coordination between other functions.

“One of our goals is to further elucidate the role of Purkinje cells in recovering from ataxia,” said Van der Heyden.

“We are particularly excited about the results of this study because we may be able to infer approaches for treating not only other motor disorders, but perhaps non-motor neuropsychiatric states,” the corresponding author said. Dr. Roy Sirito, an associate professor of pathology, said. Director of Immunology and Neuroscience at Baylor College of Medicine, and Neuropathology Core Facility at the Yan and Dan Duncan Institute for Neurology, Texas Children’s Hospital.

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