Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease by restoring striatal synaptic plasticity. The finding could pave the way for new non-drug approaches. The research was led by Catholic University, Rome Campus and A. Gemelli IRCCS Polyclinic Foundation.
Neuroscientists from the Faculty of Medicine of the Catholic University, Rome Campus, and the A. Gemelli IRCCS Polyclinic Foundation have discovered that intensive exercise has the potential to slow the progression of Parkinson’s disease. They have also described the biological mechanisms behind this finding, which could pave the way for new non-drug approaches to treatment.
The study titled “Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease by restoring striatal synaptic plasticity” has been published in the journal Science Advances. Led by researchers from the Catholic University, Rome Campus, and the A. Gemelli IRCCS Polyclinic Foundation, the study involved collaboration with various research institutes including the San Raffaele Telematic University Rome, CNR, TIGEM, University of Milan, and IRCCS San Raffaele, Rome.
The research received funding from the Fresco Parkinson Institute at New York University School of Medicine and The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders, as well as the Ministry of Health and MIUR. The study identified a previously unknown mechanism responsible for the positive effects of exercise on brain plasticity.
Dr. Paolo Calabresi, Full Professor of Neurology at the Catholic University and director of the UOC Neurology at the University Polyclinic A. Gemelli IRCCS, who served as the corresponding author, commented on the findings. He said, “We have discovered a never observed mechanism, through which exercise performed in the early stages of the disease induces beneficial effects on movement control that may last over time even after training is suspended. In the future, it would be possible to identify new therapeutic targets and functional markers to be considered for developing non-drug treatments to be adopted in combination with current drug therapies.”
Prior studies have indicated a connection between intensive physical activity and increased production of the brain-derived neurotrophic factor (BDNF), a critical growth factor. The researchers were able to replicate this phenomenon in an animal model of early-stage Parkinson’s disease through a four-week treadmill training protocol. They demonstrated, for the first time, how BDNF contributes to the positive effects of physical activity on the brain.
The study, led by Dr. Gioia Marino and Dr. Federica Campanelli, researchers at the Faculty of Medicine, Catholic University, Rome, employed a multidisciplinary approach using various techniques to measure improvements in neuronal survival, brain plasticity, motor control, and visuospatial cognition. The primary outcome observed from daily treadmill training sessions was a decrease in the spread of pathological alpha-synuclein aggregates. In Parkinson’s disease, these aggregates lead to the gradual dysfunction of neurons in specific brain areas crucial to motor control, namely the substantia nigra pars compacta and the striatum.
The neuroprotective effect of physical activity is associated with the survival of dopamine-releasing neurons and the subsequent ability of striatal neurons to express a form of dopamine-dependent plasticity. These aspects are typically impaired in Parkinson’s disease. Consequently, animals that underwent intensive training maintained motor control and visuospatial learning, which rely on the activity of the nigrostriatal pathway.
Neuroscientists also discovered that BDNF, which increases with exercise, interacts with the NMDA receptor for glutamate. This interaction enables efficient neuronal responses to stimuli in the striatum, with effects that persist beyond the exercise regimen.
Dr. Paolo Calabresi elaborated on the research team’s involvement in a clinical trial to assess whether intensive exercise can help identify new markers for monitoring disease progression in early-stage Parkinson’s patients. The trial also aims to determine the disease’s progression profile. Given the significant neuroinflammatory and neuroimmune components of Parkinson’s disease, particularly in its early stages, the research will continue to investigate the role of glial cells. These specialized cells provide physical and chemical support to neurons and their environment. The aim is to identify the molecular and cellular mechanisms underlying the observed beneficial effects.