International Business Department           Liu Bojia           August 9, 2023

  Parkinson's disease is a common neurodegenerative disorder in which patients may experience cognitive and mood changes in addition to motor dysfunction. Scientists have been searching for ways to improve the symptoms of Parkinson's disease, although progress in research on therapeutic drugs is still limited. In addition to developing new drugs, some researchers have focused on non-drug means.

  A number of clinical studies have shown that physical exercise appears to be effective in improving Parkinson's-related movement disorders, such as a paper in last year's Annals of Neurology, which noted that aerobic exercise can slow the progression of Parkinson's disease patients, who experience enhanced functional connectivity between the anterior crustal nucleus and the motor cortex, better cognitive performance, and an increase in dopamine release from the caudate nucleus after adhering to aerobic exercise.

  Recently, research in Science Advances has once again added new evidence that exercise improves Parkinson's disease, with a collaboration of research institutions from Italy finding that adherence to high-intensity exercise, similar to running, restores neuronal synaptic plasticity in the striatum and improves motor and cognitive deterioration caused by the disease.

  According to the authors' description, this type of exercise regimen can be beneficial in the early stages of the disease, and in particular can help improve motor control. This benefit is retained after a period of exercise suspension.

  Misfolding of the alpha-synuclein (α-syn) protein, as well as the aggregation of toxic proteins, can severely impair the function of dopaminergic neurons and is one of the pathological hallmarks of Parkinson's disease. Whereas some past studies have shown that mice can reduce the propagation rate of α-syn in the brain after treadmill exercise, more mechanisms remain unclear.

  To unravel the mystery, the research team reconstructed a batch of Parkinson's disease model mice in which they injected preformed fibers (PFF) of α-syn into the striatum of the mice. In the absence of external intervention, neurons in the mice's striatum lose their long-term gain capacity (an effect that occurs when neuronal synaptic signaling is persistently enhanced) and produce abnormal neural activity, and the mice progressively experience developing motor and behavioral deficits.

  In the experiment, some of the mice were placed on a treadmill for a period of 4 weeks, in addition to a control group with no intervention. The treadmill training had a strict control, the exercise time was set at 30 minutes, while the running speed was uniform, and the mice were subjected to slight electrical stimulation when it was too fast or too slow, so as to ensure that the exercise intensity obtained by each mouse was basically the same.

  After 4 weeks, the authors could clearly observe that those mice that participated in the exercise performed better in motor control and visuospatial learning, whereas the mice in the "sedentary" group, which had no intervention, were not so lucky, and their motor deficits were obvious.

  In terms of underlying mechanisms, they also observed that exercise slowed down the propagation of alpha-synuclein aggregates in the brains of the mice, and that this change rescued dopaminergic neurons in the striatum, which survived at a much higher rate in the exercise group than in the control group, and maintained the functional integrity of the neuronal synapses. The "sedentary" mice showed a significant decrease in synaptic plasticity due to excessive aggregation of α-syn.

  In addition to better performance of the neurons themselves, the exercising mice had higher levels of neurotrophic factors that bind to glutamate receptors and enhance the response of striatal neurons to signaling stimuli.

  The team is currently advancing a clinical study for identifying which molecules have a role in slowing disease progression under high-intensity exercise. The authors say that these results will lead us in the future to more appropriate non-pharmacological ways of controlling Parkinson's disease and improving the quality of life for patients.