Vigorous Exercise Helps Slow Parkinson's Symptoms in Rats

Neuroscientists from the Faculty of Medicine and Surgery of the Catholic University and the Agostino Gemelli University Hospital Foundation IRCCS  have discovered that intensive physical exercise could slow down the course of Parkinson's disease and have also understood the underlying biological mechanisms. This important discovery could open the way to new non-pharmacological approaches.

It is the result of a study entitled "Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson's disease restoring striatal synaptic plasticity" published in the prestigious journal Science Advances which involves, in addition to the Catholic University, the Rome campus and the A. Gemelli Polyclinic Foundation IRCCS, various research institutes: San Raffaele Telematic University of Rome, CNR, TIGEM, University of Milan, IRCCS San Raffaele Rome.

The research, made possible by funding from the Fresco Parkinson Institute to New York University School of Medicine and The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders , the Ministry of Health and the MIUR (both relating to the 2017 PRIN call and those CNR-MUR, two different grants), has identified a new mechanism responsible for the positive effects of physical exercise on brain plasticity.

Previous work has shown that intensive physical activity is associated with an increase in the production of a growth factor essential for the survival of neurons, the Brain-Derived Neurotrophic Factor (BDNF).

In this study, the authors observed the same phenomenon in response to a treadmill training protocol and for the first time demonstrated the mechanism through which this neurotrophic factor acts in determining the beneficial effects of physical activity on a cerebral and therefore behavioral level. 

So the experts demonstrated that a four-week exercise protocol can slow disease progression in an animal model of early-stage Parkinson's (obtained by intracerebral administration of human alpha-synuclein, a protein that in its aggregate form plays an important role in the disease).

The study, whose main authors are Drs Gioia Marino and Federica Campanelli , researchers at the Faculty of Medicine and Surgery of the Catholic University, Rome campus, used various techniques to measure a neuroprotective effect of physical exercise on motor behavior and visual-spatial cognition.

The main effect, observed in response to daily treadmill training for four weeks, was a reduction in the spread of pathological alpha-synuclein aggregates, which in Parkinson's disease leads to the gradual and progressive degeneration of nerve cells in certain areas brain (the substantia nigra pars compacta and the striatum - the so-called nigrostriatal pathway), responsible for movement control.

The neuroprotective effect of motor activity is associated with the survival of neurons that release the neurotransmitter dopamine and with the ability of neurons in the striatum to continue performing their function, aspects otherwise compromised by the disease.

Motor control and visuo-spatial learning, functions dependent on nigrostriatal activity, are also intact in animals subjected to intense training.

Neuroscientists also discovered that BDNF, which increases with exercise, interacts with the NMDA glutamate receptor, allowing neurons in the striatum to respond effectively to stimuli, with effects that persist over time beyond the disruption. of exercise.

As regards the possible developments of this research, Professor Paolo Calabresiadds that: «Our research group is involved in a clinical study to verify whether physical exercise can slow the progression of Parkinson's disease in early-stage patients and to identify new markers capable of following the course of the disease. Considering that Parkinson's disease is characterized by an important neuroinflammatory and neuroimmune component, which plays a key role in the early stages of the disease, the research will continue thanks to the decisive contribution of animal models, which will also allow us to investigate the involvement of the cells of the glia, cell populations that support the activity of neurons, as well as being implicated in the immune response. This will make it possible to identify molecular and cellular mechanisms underlying the observed beneficial effects."

Reference: Marino G, Campanelli F, Natale G, et al. Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity. Sci Adv. 2023;9(28):eadh1403. doi:10.1126/sciadv.adh1403

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