Growth factor erythropoietin promotes protective myelin formation, showing therapeutic potential

In the brain, it is not only important that nerve cells send signals, but also how quickly they can do so. In order for information to flow smoothly, a kind of biological insulation is necessary. The brain forms specialized cells called oligodendrocytes for this purpose. They coat the long extensions of nerve cells, the axons, with a protective layer of myelin.

Similar to the insulation of power cables, this layer ensures that electrical signals are transmitted efficiently and quickly. Without the help of oligodendrocytes, the brain would be slower, more susceptible to malfunctions and many complex functions of thinking, feeling and moving would hardly be possible.

Influence of EPO on the development and maturation of oligodendrocytes

Researchers at the Max Planck Institute for Multidisciplinary Sciences in Göttingen and the Central Institute of Mental Health (CIMH) in Mannheim have discovered a previously unknown influencing factor on these specialized cells.

A team led by Prof. Dr. Dr. Hannelore Ehrenreich and Prof. Dr. Klaus-Armin Nave was able to show in experiments on mice that the growth factor erythropoietin (EPO), known from hematopoiesis, promotes the development and maturation of oligodendrocytes—from immature precursor cells to fully mature myelin-forming cells. What is particularly exciting is that the body’s own EPO, which is produced in the brain during mental or physical exertion, also shows similar effects.

“We were able to prove that EPO stimulates the development of oligodendrocytes and thus supports the formation of the protective myelin layers around nerve cells. Interestingly, EPO not only acts as an external drug, but is also produced by the body itself, for example through physical or mental activity,” says Prof. Dr. Dr. Hannelore Ehrenreich, head of Experimental Medicine at the CIMH and last author of the study published in Nature Communications.

“This confirms our hypothesis that exercise and cognitive activity can directly improve the structure of the brain via the EPO system,” adds Prof. Dr. Klaus-Armin Nave, Director at the Max Planck Institute for Multidisciplinary Sciences.

Through specific analyses of individual cell nuclei (single-nuclei RNA sequencing), the scientists found numerous genes that are activated or suppressed by EPO—many of which are related to cell maturation, signaling and cognitive abilities. In addition, mice lacking a specific EPO receptor in mature oligodendrocytes showed slight disturbances in the myelin structure of the hippocampus—an area that is important for learning and memory. These animals also performed worse in demanding memory tests.

New therapeutic approaches

The results suggest that EPO is not only useful for blood formation, which is how it got its name, but also plays a key role in learning and thought processes. As EPO is already approved as a drug and can be produced naturally in the body, this opens up new therapeutic perspectives.

“In the future, EPO could help treat cognitive disorders or neurodegenerative diseases such as Alzheimer’s—either as a drug or through targeted activation of the body’s own EPO system, for example through motor-cognitive training,” says Prof. Ehrenreich.

Provided by
Zentralinstitut für Seelische Gesundheit