With the number of older individuals estimated to double by the year 2050 globally, a better understanding of how the brain ages is needed to inform personal and policy-level decisions regarding our health and economic wellbeing. Prior research suggests that deficits in cognitive control -- our critical ability to switch between goals and strategies -- emerge with age, but questions remain about its developmental trajectory and whether these deficits can be mitigated by lifestyle interventions, such as regular exercise.
Exercise is a powerful way to improve almost every aspect of brain functioning, but the underlying molecular mechanisms are less clear. We have shown that 12 days of voluntary wheel running in rats improves cognitive control abilities and is associated with increases in the number of dendritic spines on neurons in the frontal lobe. Trophic factors such as brain-derived neurotrophic factor and vasculature endothelial growth factor are believed to support this enhanced structural plasticity, but the extent to which exercise changes the expression of trophic factors in frontal brain regions remains unexamined. Additionally, evidence suggests that mitochondrial dysfunction contributes to numerous age-related neuropsychiatric conditions and has been shown to increase with age.
In AIM 1 we will first establish whether 12 days of voluntary wheel running is sufficient to improve cognitive control performance using a rodent variant of the canonical stop-signal task. In AIM 2 we will use a spatial transcriptomic approach to survey changes in trophic support and mitophagy in the frontal brain areas of aged rats with or without exercise experience. Ultimately, we hope to characterize these molecular changes in the anterior cingulate cortex, the medial prefrontal cortex, and the dorsal medial striatum, a well-defined circuit known to be critical for cognitive control with an eye towards identifying how this circuit changes and support brain health across the lifespan.
