The short commentary here reports on an investigation of the benefits of exercise as a compensatory therapy to reduce the impact of Parkinson's disease. Physical activity and physical fitness produce benefits that are on a par with many pharmaceutical and other therapies when it comes to the progression of age-related diseases. This is as much a judgement on the feeble, marginal nature of so much of present day medicine as it is a statement on the merits of exercise. These therapies are marginal because they fail to tackle the root causes of aging. They attempt to influence the downstream, failing state of cellular activity and metabolism. It is akin to changing the oil in an old engine and pressing the accelerator harder rather than replacing the problem parts.
Physical exercise has repeatedly been demonstrated to alleviate comorbidities associated with aging, and to contribute to reducing an individual's risk of developing neurodegenerative conditions such as Parkinson's disease (PD) or Alzheimer's disease (AD). Evidence has accumulated to suggest that exercise can ameliorate many of the symptoms of PD, not only the motor dysfunction, but also some of the non-motor symptoms (NMS), such as cognitive impairment and depression.
In order to decipher the cellular and molecular mechanisms underlying the potential beneficial effects of exercise in PD, it is necessary to employ animal models. The most common models used by the scientific community focus on replicating the motor symptoms of the disease, by applying a chemical lesion in order to cause degeneration of the dopaminergic pathway, which is responsible for controlling movement. However, such models are not useful for examining the NMS, which typically involve several different neurotransmitter pathways and multiple regions of the brain. A recently-developed animal model, involving induction of α-synuclein overexpression in the adult rat brain using adeno-associated viral (AAV) vectors, is widely considered to most consistently reproduce the pathological features and progressive neurodegeneration associated with human PD.
Adult male rats were given free access to running wheels in cages (voluntary exercise) from one week after administration of AAV-α-synuclein into the substantia nigra. We found that voluntary exercise had no effect on motor function or on dopaminergic neuronal loss in the substantia nigra. However, overexpression of α-synuclein significantly impaired the ability of the animals to perform hippocampal-associated cognitive tasks. This was associated with deficits in hippocampal neurogenesis, a form of neuroplasticity and a key cellular process underlying learning and memory. Importantly, voluntary exercise protected against this cognitive dysfunction, and this protective effect was mediated, at least in part, by alterations in neurogenesis levels.
This is the first study to date that has employed the AAV-α-synuclein model to investigate exercise as a therapeutic intervention, and its strength lies in the fact that this model is widely accepted to be the most similar to the progressive nature of the human condition. It must be appreciated that there are difficulties associated with measuring the effects of exercise in patients, as well as in animal models, that have problems with their motor function. Nevertheless, all of the available evidence suggests a growing rationale for including structured exercise programs as part of a patient's therapeutic regimen.