A recent study suggests that the brain-boosting benefits typically associated with exercise, specifically the generation of new neurons, may not require physical activity at all. Researchers from the University of Illinois Urbana-Champaign have found that microscopic packages known as extracellular vesicles (EVs) released during exercise can be transferred between individuals, potentially enhancing neurogenesis—the process of new neuron formation—in the brain.
During physical activity, the body releases thousands of molecules into the bloodstream, including EVs that contain proteins, RNA, fats, and other signaling molecules. These tiny vesicles are capable of crossing the blood-brain barrier, making them instrumental in promoting neurogenesis, particularly in the hippocampus, a region known for its role in memory and learning. However, a crucial question remained: could these exercise-derived vesicles effectively stimulate neurogenesis when administered to individuals who had not exercised?
To investigate, the research team conducted an experiment involving adult male mice. One group of mice had unrestricted access to running wheels for four weeks, while a second group remained sedentary with their wheels locked. After the four-week period, the scientists collected blood samples from both groups and isolated the EVs, categorizing them into two types: exercise-derived EVs (ExerVs) and sedentary-derived EVs (SedVs).
Another set of sedentary mice received either the ExerV, SedV, or a placebo injection of phosphate-buffered saline. The results were compelling. The sedentary mice that received ExerVs exhibited a significant increase in the density of new cells, with approximately 89.4% of these cells differentiating into neurons, identified by the presence of NeuN markers. Further analysis using bromodeoxyuridine (BrdU) labeling revealed that the ExerVs group had around 50% more BrdU-positive neurons compared to the control groups, suggesting that the benefits were specific to the exercise-derived EVs.
The researchers confirmed these findings through a second cohort, reinforcing the notion that it is indeed the EVs, rather than genetic factors, that drive the generation of new neurons. “Our findings demonstrate that systemically administered ExerVs robustly enhance adult hippocampal neurogenesis by approximately 50% in sedentary mice,” the team stated. They emphasized that despite the increase in neuron production, there were no significant alterations to the overall structure of the hippocampus, supporting previous research that indicates a balance between neuron growth and natural pruning processes.
The implications of this research are noteworthy. While animal studies typically have limitations, the potential for EV-based therapies to benefit individuals with restricted physical activity—due to injuries, neurological diseases, or frailty—presents an exciting avenue for future exploration. The researchers plan to investigate whether these EVs can enhance cognitive functions such as learning and memory or provide protective benefits against neuronal degradation associated with conditions like depression, post-traumatic stress disorder (PTSD), and Alzheimer’s disease.
“These findings suggest that systemically delivered ExerVs are sufficient to enhance hippocampal neurogenesis but do not affect vascular coverage,” the researchers noted. They believe that ExerVs could represent a promising therapeutic strategy for conditions characterized by hippocampal atrophy, given their ability to boost adult neurogenesis. Further studies are warranted to elucidate the mechanisms linking the administration of peripheral ExerVs to increased neurogenesis and to assess whether this enhancement can restore cognitive function in scenarios of hippocampal damage.
The research was published in the journal Brain Research, highlighting a significant step towards understanding the potential of exercise-derived molecules in enhancing brain health.