Recent research from the University of Illinois Urbana-Champaign has uncovered that the beneficial impact of exercise on brain health, specifically the growth of new neurons, may not require physical movement. Instead, it appears that microscopic “packages” known as extracellular vesicles (EVs) released into the bloodstream during exercise can be transferred to sedentary individuals, potentially providing similar neurological benefits.
During exercise, the body releases thousands of molecules into the bloodstream, including EVs filled with proteins, RNA, fats, and other signaling molecules. These vesicles are small enough to cross the blood-brain barrier, promoting neurogenesis—the formation of new neurons—in the hippocampus, a region crucial for memory and learning. Researchers sought to determine whether these exercise-stimulated vesicles could still promote neuron growth in individuals who had not exercised.
To explore this, the research team conducted an experiment involving adult male mice. One group had continuous access to running wheels for four weeks, while a second group remained sedentary, with their wheels locked. Following this period, blood samples were collected from both groups, allowing the researchers to isolate EVs into two categories: exercise-derived EVs (ExerVs) and sedentary-derived EVs (SedVs).
In a subsequent phase, additional sedentary mice were randomly assigned to receive either ExerVs, SedVs, or a placebo injection. The results were significant. Mice receiving the ExerV transfusion exhibited a marked increase in the density of new cells, with an impressive 89.4% of these new cells differentiating into neurons, as indicated by the presence of the NeuN protein.
The researchers further assessed the generation of neurons in the dentate gyrus, a part of the hippocampus associated with lifelong neuron production, using bromodeoxyuridine (BrdU) labeling—a method that acts as a molecular timestamp for newly formed cells. Findings showed that the ExerVs group had approximately 50% more BrdU-positive neurons compared to the control groups. In contrast, the SedV-treated mice demonstrated minimal differences from those receiving the placebo, highlighting the specific role of exercise-induced EVs in promoting neuron growth.
“Our findings demonstrate that systemically administered ExerVs robustly enhance adult hippocampal neurogenesis by approximately 50% in sedentary mice,” the researchers stated. They emphasized that this result was consistently replicated across two independent cohorts, underscoring the reliability of their observations.
Importantly, despite the increase in new neurons from the ExerV transfusion, there were no significant alterations in the overall structure of the hippocampus. This aligns with previous findings that suggest the growth of exercise-induced neurons is balanced by natural processes, such as pruning, where the brain eliminates underperforming neurons and synapses.
The implications of this research extend beyond animal studies. While the authors caution about the normal limitations of such research, they suggest that if these findings can be replicated in humans, EV-based therapies could provide significant benefits to individuals with limited physical activity due to injury, neurological diseases, or age-related frailty.
Next steps for the research team include investigating whether these EVs can enhance cognitive functions such as learning, memory, and stress processing. They also aim to determine if ExerVs can protect the brain from neuron degeneration related to conditions like depression, post-traumatic stress disorder (PTSD), and Alzheimer’s disease.
“ExerVs may represent a promising therapeutic strategy for conditions marked by hippocampal atrophy, given their ability to enhance adult neurogenesis,” the researchers concluded. They stressed the need for future studies to elucidate the mechanisms linking peripheral ExerV administration to increased neurogenesis and to evaluate whether these enhancements can restore cognitive function in cases of hippocampal damage.
The complete study is published in the journal Brain Research.
