Increased performance for the thinking organ: Erythropoietin (EPO), known as a doping agent, also works in the brain. As experiments with mice reveal, the messenger substance is increasingly released there when the cognitive load is particularly high. As a result, the nerve cells network more effectively – and new brain cells are even formed. The signal for EPO production is a slight lack of oxygen in the cells.
Erythropoietin (EPO) is a notorious doping agent. But the hormone also occurs naturally in the human body. It is released when there is a lack of oxygen in the organism and then stimulates, among other things, the formation of new red blood cells. This improves oxygen absorption and, as a result, physical performance.
In adults, EPO is mainly formed in the kidney – this has been known for a long time. “Surprisingly, researchers later also detected EPO and its receptor in the brain,” explains Debia Wakhloo from the Max Planck Institute for Experimental Medicine in Göttingen and her colleagues. There, the growth factor also seems to have a protective and performance-enhancing effect, as practical experience suggests.
Motor challenge for mice
“The administration of EPO improves regeneration after a stroke and thus reduces the damage to the brain. Patients with mental disorders, which we treated with EPO, are also significantly more efficient, ”reports Wakhloo’s colleague Hannelore Ehrenreich. This effect is known for example from people with schizophrenia, depression or multiple sclerosis.
But how can this effect be explained? Or to put it another way: what exactly causes erythropoietin in our thinking organ? To find out, the scientists have now carried out experiments with mice. For their study, they first had adult mice trained on wheels – under difficult conditions, because the spokes of the wheels were arranged at irregular intervals. The background: “Running in these bikes requires you to learn complex movements that are particularly challenging for the brain,” explains Ehrenreich.
It learns faster with EPO
Would EPO treatment affect how rodents do this? The results revealed that after the animals were given the growth factor, they learned the movements required for the wheels faster. In addition, they were much more resilient.
Further examinations provided the explanation for this effect. The researchers found that after treatment, the mice formed around 20 percent more nerve cells in the so-called pyramid layer of the hippocampus – a brain region that is crucial for learning and memory. “In addition, the nerve cells network better and faster with other nerve cells and thus exchange signals more efficiently,” reports Ehrenreich.
Slight lack of oxygen as a trigger
Erythropoietin therefore seems to promote the formation and networking of nerve cells in the brain. But under what conditions is the messenger released there? The researchers also found this out in their experiments: As is known from the rest of the body, the release of EPO in the brain is linked to a lack of oxygen.
Apparently this happens when nerve cells need more oxygen than they normally have when learning complex tasks. The slight lack of oxygen caused in this way serves as a signal for increased EPO release. In the experiment, the expression of this messenger substance and its receptors was increased after a few hours under difficult conditions in the impeller, as the team reports.
“Self-reinforcing process”
“This is a self-reinforcing process: mental effort leads to mild hypoxia, which in turn stimulates the production of EPO and its receptors in the correspondingly active nerve cells. EPO then increases the activity of these nerve cells, causes new neurons to form from neighboring progenitor cells and increases their complex networking, ”summarizes Ehrenreich.
It is interesting that oxygen deficiency is, according to the common assumption, something harmful. “However, more recent considerations also consider potentially useful effects and protective functions. Our data suggests that hypoxia can act as a driving force for neural plasticity, ”the researcher and her colleagues state.
Targeted performance increase?
If the now deciphered cycle of action also exists in humans, this could explain why learning new, demanding skills can increase our mental fitness. The extent to which additional erythropoietin can help is unknown. It is better to avoid “brain doping” using EPO.
At the same time, the researchers’ findings confirm recent findings that new nerve cells can also form in the adult brain. “The generation of pyramid neurons from existing progenitor cells by EPO influence may be a previously overlooked aspect of adult neurogenesis,” explains the team. (Nature Communications, 2020; doi: 10.1038 / s41467-020-15041-1)
Source: Max Planck Society for the Advancement of Science e.V.
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