Stress hormone turned out to be a participant in brain repair

The observations began with a simple but persistent question. After experimental brain damage in laboratory mice, an active group of cells steadily appeared near the injury site, the nature of which remained unclear for a long time. A young researcher, Clemens Rees, who was then a graduate student at the Max Planck Institute of Psychiatry, took up the task.

A step-by-step analysis showed that we are talking about oligodendrocyte progenitor cells, or OPCs. These cells eventually turn into oligodendrocytes, which form the myelin sheath of axons. Myelin is necessary for the normal transmission of nerve signals and the supply of nutrients to neurons. Its loss underlies multiple sclerosis and accompanies brain injury.

In the course of the work, the researchers confirmed that after damage to the OPC, they actively multiply, then mature and restore the myelin layer. But the main discovery was something else. About a third of these cells near the wound began to synthesize CRH. Previously, it was believed that OPCs are not capable of producing neuropeptides of this type.

CRH production started within a few hours of injury and stopped after about three days. Such short-term activity indicates the fine-tuning of the early stages of healing. Additional experiments have shown that the CRHR1 receptor located on another OPC subgroup plays an important role in this process. In its absence, the cells divided faster, but matured worse, and as a result, fewer stable oligodendrocytes were formed. Myelin was restored less efficiently.

This mechanism turned out to be significant not only for injuries. OPCs are actively involved in the myelination of the brain after birth, the process continues until early adulthood. Scientists have found that CRHR1 regulates this stage of development as well. In models without this receptor, an excessive number of OPCs formed in the early stages, which eventually led to changes in the structure of myelin in the adult brain, especially on thin axons.

A logical question arose: where does CRH come from in the developing brain if there is no damage. The researchers suggest that during this period, the hormone comes from neurons and controls the balance between division and OPC maturation.

The discovery has broader implications. It is known that CRH is actively released under stress, especially at an early age, and chronic stress increases the risk of mental disorders. According to the head of the study, Jan Deussingh, the CRH system in oligodendrocyte progenitor cells may play a more significant role in depression and other stress-associated conditions than previously thought.