Effects of Aging and Exercise Training on Cerebrovascular Vasomotor Reactivity, Depressive Behavior, and the Hippocampal Transcriptome
The aging global population is experiencing an increased prevalence of cerebrovascular diseases, such as stroke and dementia. This highlights a need for understanding the pathophysiological mechanisms of age-related cerebrovascular alterations, alongside benefits of interventions such as physical activity. Therefore, our aims were to 1) examine the impact of aging and exercise training on cerebrovascular function, and 2) to characterize age- and exercise training-related changes in the hippocampus transcriptome. Methods: Young and old male rats were randomized to a sedentary condition or exercise training for 10 weeks. In the first protocol, cerebral arteries were isolated to test vasomotor reactivity, quantify gene/protein expression, and to assess nitric oxide production. In the second protocol, anhedonia was assessed and hippocampal tissue collected for RNA-sequencing. Bioinformatic analyses (i.e., protein-protein interaction mapping) were performed. Results: Aging impaired endothelium-dependent vasoreactivity in the posterior communicating artery (PCoA), with a shift from endothelial NOS- to neuronal NOS-mediated vasorelaxation, and alterations in oxidative stress production. In support, PCoA superoxide-mediated vasoreactivity and nNOS-mediated production of NO increased with age. Exercise enhanced vasodilation in young rats, but results suggested reduced cerebrovascular plasticity in older animals. In the second protocol, exercise training attenuated the age-related increase in anhedonia behavior. Hippocampal RNA-sequencing revealed altered inflammatory and oxidative stress pathways with aging that were mitigated by exercise training. Conclusions: Our findings underscore the complex interplay between vascular/neuronal factors in the aging brain. Furthermore, these findings highlight the therapeutic potential of exercise in mitigating the adverse effects of aging on cerebral health Overall design: Bulk RNA-sequencing of hippocampal tissue in young/old sedentary/trained rats.