Identifying Physical Activity-Associated Neuroprotective Gene Transcripts

Abstract

Mild, moderate, and vigorous physical activity are associated with decreased risks of Alzheimer’s disease, Parkinson’s disease, and a decreased infarct from stroke. Physical activity increases neurogenesis in the hippocampus and upregulates neurotrophic factors throughout the brain, but it largely has been understudied in motor brain regions related to Parkinson’s disease. We hypothesized that aerobic exercise would be protective against a MPTP lesion in Rhesus monkeys. We used three cohorts of monkeys to study gene expression associated with physical activity and exercise in motor regions of the brain: (1) spontaneously physically active rhesus monkeys, (2) exercised rhesus monkeys, and (3) spontaneously physically active and exercised rhesus monkeys before and after receiving a MPTP lesion. We found that physical activity as measured by accelerometers predicts the size the MPTP lesion, as monkeys with high levels of physical activity were protected from the lesion. Furthermore, the activity-associated neuroprotective gene expression signature involved transcripts associated with chromatin remodeling, neuronal survival, and specifically syntaxin 3. These studies suggest that being physically active is protective against Parkinson’s disease.