Exercise Reduces Parkinson's Disease Morbidity

neurons


Two studies suggest exercise may reduce risk of Parkinson's Disease and reduce the behavioral effects after onset.







Parkinson's disease affects over a million Americans is the second most prevalent neurodegenerative disease following Alzheimers disease.  Parkinson's disease is a dopaminergic brain disorder that leads to slow movements (bradykinesia), rigidity, tremor and postural instability. Parkinsons patients often develop problems with speech, memory, general cognition and smell.  As a result of these symptoms, Parkinson's disease is a dehibilating disease burdening life for both patient and family. However, patients can remain functional with treatment for over 30 years after diagnosis, it is a slowly progressing disease unlike some other neurodegenerative diseases. Parkinson’s disease results from a loss of dopaminergic neurons in the substantia nigra (a region in the midbrain of the brainstem). An etiology is not known, although several genes have been implicated including alpha-synuclein (which forms lewy bodies in neurons, a pathologic characteristic of Parkinsons) and DJ1 (related to mitochondria function). Reactive oxygen species, calcium signaling, proteinaupathy, and viruses have all been discussed as possible etiologies. Several different treatments are available to mask the symptoms, but there is currently no cure. These treatments include dopamine (prescribed as Levodopa), dopamine agonists (Mirapex) and deep brain stimulation (DBS).

In 2010, a study was published finding that adults who participated in physical activity had a reduced risk of developing parkinson's disease in the next four to ten years (Physical Activities and Future Risk of Parkinson Disease, 2010, Q. Xu, Y. Park, et al.). This study looked at the physical activity of 200,000 plus participants in a NIH-AARP study. Doctor diagnosed Parkinson's disease rates were collected ten years later. Those who were diagnosed with Parkinson's in the four years immediately following the initial physical activity survey were left out of the statistical analysis. The study found that adults who reported participating in physical activity over each of the two survey periods had a 40% lower risk of being diagnosed with Parkinson's disease ten years later.  Interestingly, the study found that physical activity at early ages had no link to risk of developing Parkinson's. Exactly why physical activity is correlated with a reduced risk of developing Parkinson's is not exactly known. Most likely, exercise was delaying onset of symptoms and progression of disease, rather than fully preventing diagnosis. However, several studies provide some light on possible explanations.

A study published in 2003 found that mice forced to run on a treadmill after being injected with a dopamine toxin, 6-hydroxydopamine, showed less loss of motor control and better retention of neurochemicals that play a role in the dopamine pathway (Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson's disease, 2003, J.L. Tillerson, et al.).

The study looked at the levels of DAT, VMAT2 (vesicular monamine transporter) and TH (tyrosine hydoxalase). DAT is responsible for dopamine re-uptake in the synapse.  VMAT2 is responsible for the vesicle that transports dopamine between the synapses. TH is the rate-limiting enzyme in the synthesis of dopamine. Studies have shown that people with Parkinson's have reduced levels of VMAT2. When mice were treated with the toxin MPTP significant decreases in VMAT2, DAT and TH were observed.  However, as figure A shows, mice forced to run on a treadmill showed a reduced drop in DAT, VMAT2 and TH.

Figure A. Mice treated with MPTP had significant losses of neurochemicals DAT, VMAT2 and TH relative to the control.  However, mice treated with MPTP and forced to run on a treadmill showed less loss of all three measured neurochemicals.

In addition, motor function was measured in the neurotoxin-treated mice using a forepaw test. Parkinsons-model mice running on a treadmill showed significantly better performance in motor function than sedentary mice. This suggests that exercise could be used to reduce the behavioral consequences of Parkinson's disease.

In summary, a large human study demonstrated exercise reduces risk of being diagnosed with Parkinson's disease over the next ten years. In addition, a study of mice treated with a parkinsons-inducing neurotoxin found that exercise reduced dopamine neurochemical drop and motor function. Researchers will find a cure for parkinson’s disease, but in the meantime exercise may be the only option for delaying the progression.



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