A single-cell transcriptomic analysis of the mouse hippocampus after voluntary exercise
Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after four weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-?B, Wnt/ß-catenin, Notch, retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline. Overall design: 8 WT adult mice were divided into 2 equally sized groups - runners that had free and voluntary access to running wheels in their cages (the 'exercise' group), and sedentary mice that had similar wheels in their cages that were however blocked (the 'control' group). This voluntary exercise paradigm lasted 4 weeks, after which whole hippocampal nuclei were isolated from all mice for snRNA-seq analysis.