Neuroscientists from the Faculty of Medicine of the Catholic University, Rome Campus, and from the A. Gemelli IRCCS Polyclinic Foundation have discovered that intense physical exercise could slow down the course of Parkinson’s disease. The discovery could pave the way for new non-pharmacological approaches.
The results of the study were published in the scientific journal Science Advances.
Parkinson’s disease: Here’s why vigorous exercise is important
The research was conducted by the Catholic University, Rome Campus and by the A. Gemelli IRCCS Policlinico Foundation, in collaboration with various research institutes including the San Raffaele Telematic University of Rome, the CNR, the TIGEM, the University of Studies in Milan and the IRCCS San Raffaele in Rome. Research has identified a new mechanism responsible for the positive effects of exercise on brain plasticity.
The corresponding author, Full Professor of Neurology at the Catholic University and Director of the UOC of Neurology at the A. Gemelli University Hospital IRCCS Paolo Calabresi, stated: “We have discovered a mechanism never observed before, through which the exercise performed in early stages of the disease induces beneficial effects on movement control that can persist over time even after training is stopped.”
“In the future, it would be possible to identify new therapeutic targets and functional markers to be considered for the development of non-pharmacological treatments to be adopted in combination with current pharmacological therapies,” he added.
Previous work has shown that vigorous physical activity is associated with increased production of a critical growth factor, brain-derived neurotrophic factor (BDNF).
The authors were able to reproduce this phenomenon in response to a four-week treadmill training protocol in an early-stage Parkinson’s disease animal model and demonstrate, for the first time, how this neurotrophic factor drives the effects benefits of physical activity in the brain.
The study, whose lead authors are Drs. Gioia Marino and Federica Campanelli, researchers at the Faculty of Medicine of the Catholic University of Rome, provide experimental support to the neuroprotective effect of exercise using a multidisciplinary approach that employs different techniques to measure improvements in neuronal survival, brain plasticity, in motor control and visuospatial cognition.
The main effect observed in response to daily treadmill exercise sessions is a reduction in the spread of pathological alpha-synuclein aggregates, which in Parkinson’s disease leads to the gradual and progressive dysfunction of neurons in specific brain areas (the substantia nigra pars compacta and the striatum, which forms 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 otherwise compromised by the disease.
Consequently, motor control and visuospatial learning, which depend on nigrostriatal activity, are preserved in intensively trained animals.
Neuroscientists also discovered that BDNF, whose levels increase with exercise, interacts with the NMDA glutamate receptor, allowing neurons in the striatum to respond efficiently to stimuli, with effects that persist beyond exercise. .
Professor Paolo Calabresi said: “Our research group is involved in a clinical trial to test whether intensive exercise can identify new markers to monitor the slowing of disease progression in early stage patients and the disease progression profile. ”.
“Because Parkinson’s disease is characterized by important neuroinflammatory and neuroimmune components, which play key roles in the early stages of the disease, research will continue to investigate the involvement of glial cells, groups of highly specialized cells that provide physical and chemical support to neurons and their environment. This will allow us to identify the molecular and cellular mechanisms underlying the observed beneficial effects,” she concluded.
Another study, this time from Tel Aviv University, suggests that a therapy combining virtual reality and treadmill exercise dramatically reduces the incidence of falls among Parkinson’s disease patients by changing the behavior of the brain and promoting beneficial brain plasticity, even in patients with neurodegenerative disease.
Patients with Parkinson’s disease experience gradual neuronal loss, leading to cognitive and motor impairments that impair their ability to walk and cause debilitating, often fatal falls. The new study shows that fall rates are reduced in response to treadmill training with virtual reality.
The number of neurons fired in the prefrontal cortex is also reduced in response to the same combination. This reduction probably reflects improvements in motor control and greater automaticity of cognitively demanding tasks.
Research underlines the importance of combining cognitive rehabilitation with motor rehabilitation of patients with Parkinson’s disease.
The study was led by Prof. Jeff Hausdorff of TAU’s Sackler School of Medicine and Tel Aviv Medical Center together with colleagues Dr. Inbal Maidan of Tel Aviv Medical Center and Dr. Anat Mirelman and Prof. Nir Giladi, both of TAU’s Sackler School of Medicine and Tel Aviv Medical Center. The results were published in the journal neurology.
“In previous research, we have shown that Parkinson’s disease patients use cognitive function, which is reflected in the activation of the prefrontal cortex of the brain, to compensate for impaired motor function,” says Prof. Hausdorff. “We also demonstrated that a specific form of exercise targeting cognitive gait control, a combined treadmill workout with a virtual reality representation of obstacles in a course, leads to a significantly lower fall rate in Parkinson’s patients.
“The virtual reality walking program, in which patients have to avoid obstacles, improves the patient’s cognitive performance and thus reduces the need for prefrontal brain activity,” continues Prof. Hausdorff.
Seventeen subjects in two groups, one that combined treadmill training with virtual reality and one that used treadmill training only, underwent a six-week intervention, exercising three times a week for approximately an hour each time. The virtual reality team played a “game” where they watched their feet walk through a city environment or park.
Through play, they implicitly learned how to deal with obstacles in the virtual environment, how to plan ahead and how to do two things at the same time, i.e. deal with the cognitive challenges related to safe walking.
The other group just walked on a treadmill with no VR components or cognitive challenges. Before and after the subjects participated in the exercise programs, the researchers used functional magnetic resonance imaging to evaluate the patients’ brain activation patterns.
“The results of the study strengthen the hypothesis that training improves motor and cognitive performance through better neuroplasticity, more than what was seen with treadmill training alone,” explains prof. Hausdorff.
“Interestingly, the benefits of treadmill training with VR were specifically observed during gait conditions that require cognitive inputs (i.e., obstacle negotiation and dual task), conditions associated with falls in everyday environments .
Under these conditions, fewer neurons were needed after training with VR, while no change was seen in the group who trained walking on a treadmill without VR.”
Previous research conducted on mouse models of Parkinson’s disease suggested the importance of specific exercises for the brain. However, the new TAU study is the first to show such results in people with Parkinson’s disease.
“Exercise that focuses on motor components promotes plasticity in brain areas associated with sensory-motor integration and coordination,” says Prof. Hausdorff. “But exercise that incorporates cognitive components also stimulates changes in brain regions related to cognition. It may therefore have a greater impact on compensatory brain function and cognitive functions related to safe ambulation (i.e., walking without falling).”
“The upshot here is that even relatively late in the disease, when 60-80 percent of dopaminergic neurons have died, there is still an opportunity to promote plasticity in the brain,” concludes Prof. Hausdorff. “Furthermore, to induce specific brain changes, exercise should be personalized and targeted to a specific clinical problem.”
Treadmill training can be used to help people with Parkinson’s disease achieve better walking movements, say the researchers. In a systematic review of the evidence, Cochrane researchers concluded that treadmill training could be used to improve specific gait parameters in Parkinson’s patients.
Gait hypokinesia, characterized by slowness of movement, is a major movement disorder affecting Parkinson’s patients and can have a major impact on quality of life. More recently, health care professionals have begun incorporating exercise into treatment regimens as a useful complement to traditional drug therapies. Treadmill training is one option that can help improve movement.
The researchers analyzed data from eight studies that included 203 patients for the review, published in The Cochrane Library. They compared treadmill training versus no treadmill training, using effects on walking speed, stride length, number of steps per minute (cadence), and distance walked to measure improvement in pace. Treadmill training had a positive impact on each of these metrics, aside from cadence.
“Treadmill training appears to be a safe and effective way to improve gait in patients with Parkinson’s disease,” said lead researcher Jan Mehrholz, of the Wissenschaftliches Institut in Kreischa, Germany. “Basically, we’ve seen very few adverse effects or dropouts in patients undergoing this type of rehabilitation therapy.”
However, the researchers say the findings need to be treated with caution as they are based on a small number of small studies. “There is still a need for larger studies to establish whether treadmill training can be safely used as routine therapy for Parkinson’s patients,” Merhholz said.
“We also need to answer basic questions about how long the benefits last and what a good training program should consist of. For example, how often and for how long should patients exercise?”
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