One of the brain’s biggest benefits from exercise – the birth of new neurons – may not even require any movement. Instead, the beneficial “packages” circulating in the blood after working out can be successfully transferred to others.
When we exercise, thousands of molecules are released into the bloodstream – including extracellular vesicles (EVs), microscopic packages filled with proteins, RNA, fats and other signaling molecules. These are also small enough to cross the blood-brain barrier to trigger neurogenesis – the growth of neurons – in the hippocampus. But a key question remained: would these exercise-stimulated vesicles still work if you delivered them to someone who hadn’t exercised at all?
Researchers at the University of Illinois Urbana-Champaign have now answered that, demonstrating that these extracellular vesicles (EVs) can be taken from one body to another without losing their power.
Adult male mice were given constant access to running wheels for four weeks, while another group was kept sedentary with their wheels locked in place. At the end of the four weeks, the team collected blood from both groups and isolated EVs, which were separated into two samples, exercise-derived EVs (ExerVs) and sedentary-derived EVs (SedVs).
Another set of sedentary mice were then randomly assigned to receive either the ExerV or SedV preparation or a placebo injection (phosphate-buffered saline). The scientists found that sedentary mice that had received the ExerVs transfusion showed a significant increase in the density of new cells – and 89.4%of these new cells had differentiated into neurons (NeuN).
The researchers then assessed how many cells in the dentate gyrus, a region of the hippocampus known to generate neurons throughout life, via bromodeoxyuridine or BrdU labeling – a sort of molecular timestamp on newly formed cells. The ExerVs group had around 50% more BrdU-positive neurons than either control group. In fact, the SedV-treated mice were all but identical to the placebo group, indicating that the brain boost was specific to the exercise-induced EVs.
A second set of mice independently replicated these results, confirming that it was the EVs, not genetics, driving 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 noted. “This effect was reproduced across two independent cohorts, underscoring the reliability and rigor of the observation.”
And, importantly, even though more new neurons were being made from ExerV transfusion, there weren’t any significant changes in overall hippocampal structure. This supports previous research that found that exercise-induced neuron growth was balanced by natural processes like pruning – where the brain gets rid of underperforming neurons and synapses.
So, what does this mean for us? The normal limitations of an animal study apply, and the researchers did not test whether the increase in neurons benefited cognitive functioning in the mice. However, it’s a promising outcome for EV-based therapies that, if replicated in humans, could give people with limited physical activity due to injury, neurological disease or frailty the chance to benefit from these EVs like healthy adults.
The researchers say the next steps will be to determine whether these EVs improve learning, memory or stress processing, and whether they can shield the brain from the neuron deterioration in the hippocampus seen in conditions like depression, post-traumatic stress disorder (PTSD) and Alzheimer’s disease.
“These findings demonstrate that systemically delivered ExerVs are sufficient to enhance hippocampal neurogenesis but not vascular coverage,” the researchers noted. “ExerVs may represent a promising therapeutic strategy for conditions marked by hippocampal atrophy, given their ability to enhance adult neurogenesis. Future studies are needed to elucidate the mechanisms linking peripheral ExerV administration to increased neurogenesis, and to determine whether this enhancement can restore cognitive function under conditions of hippocampal damage.”
The research was published in the journal Brain Research.
Source: University of Illinois Urbana-Champaign via MedicalXpress
