Parkinson’s: how intense exercise helps curb the disease

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They discover how intense exercise in the early stages of Parkinson’s can protect neurons affected by the disease and delay its progression, and that training could be combined with drug therapies.

Parkinson’s is characterized by the deterioration and death of neurons that produce dopamine, a molecule that is involved in the control and coordination of movements. Although the most striking symptoms of Parkinson’s are those that affect movement, posture or balance, there are many others, such as cognitive alterations, anxiety or depression, sleep disorders, etc.

The results of a new study may offer hope for those affected by this chronic neurodegenerative disease, as they show that intense exercise could delay the progression of Parkinson’s. Specifically, a new mechanism responsible for the positive effects of exercise on brain plasticity has been identified, a finding that may contribute to the development of new therapeutic options that are not based on drugs.

The research has been led by neuroscientists from the Catholic University Faculty of Medicine, Rome Campus, and the Policlínica A. Gemelli IRCCS Foundation, in collaboration with several research institutes, including the San Raffaele Telematic University of Rome, CNR, TIGEM, University of Milan and IRCCS San Raffaele, and has been published in Science Advances.

“Exercise carried out in the early stages of the disease induces beneficial effects on movement control that can last over time”

Paolo Calabresi, Professor of Neurology at the Catholic University and Director of Neurology at the UOC at the A. Gemelli IRCCS University Polyclinic and corresponding author, stated: “We have discovered a never-before-seen mechanism through which exercise performed in the early stages of the disease induces beneficial effects on movement control that can last over time, even after stopping training.” “In the future, it would be possible to identify new therapeutic targets and functional markers to consider in developing non-pharmacological treatments to be adopted in combination with current pharmacological therapies,” he added.

Intense physical activity has already been shown in previous studies to be associated with increased production of brain-derived neurotrophic factor (BDNF), which is a key growth factor. The researchers were able to reproduce this phenomenon in response to a four-week treadmill training protocol in an animal model of early-stage Parkinson’s disease and demonstrate, for the first time, how this neurotrophic factor determines the beneficial effects of physical activity on the brain.

The study provides experimental support for the neuroprotective effect of exercise through a multidisciplinary approach using different techniques to measure improvements in neuronal survival, brain plasticity, motor and visuospatial control, and cognition.

Physical exercise has a protective effect on neurons

The main effect observed in response to daily treadmill training sessions is a decrease in the spread of pathological aggregates of alpha-synuclein, which in Parkinson’s disease leads to gradual and progressive dysfunction of neurons in specific areas of the brain (the substantia nigra pars compacta and the striatum, constituting the so-called nigrostriatal pathway), essential for motor control.

The neuroprotective effect of physical activity is associated with the survival of neurons that release the neurotransmitter dopamine and with the consequent ability of striatal neurons to express a form of dopamine-dependent plasticity, aspects that are otherwise affected by the disease. The result is that motor control and visuospatial learning, which depend on nigrostriatal activity, are preserved in animals undergoing intensive training.

Neuroscientists have also discovered that BDNF, whose levels increase with exercise, interacts with the NMDA receptor for glutamate, allowing neurons in the striatum to respond efficiently to stimuli, with effects that persist beyond exercise.

“Our research team is involved in a clinical trial to test whether intense exercise can identify new markers to monitor slowing of disease progression in early-stage patients and profile disease progression,” said Professor Paolo Calabresi.

“Since Parkinson’s disease is characterized by important neuroinflammatory and neuroimmune components, which play a key role in the early stages of the disease, we will continue to investigate the involvement of glial cells, highly specialized groups of cells that provide physical and chemical support to neurons and their environment, allowing us to identify the molecular and cellular mechanisms underlying the observed beneficial effects.”

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