Scientists have discovered an unexpected role for a well-known stress hormone in the brain.
The finding could improve our understanding of how the brain repairs damaged nerve fibers and may eventually offer clues about diseases involving myelin loss.
The research began with a simple observation at the Max Planck Institute of Psychiatry.
Neurobiologist Jan Deussing repeatedly noticed that a group of cells gathered around damaged areas in the brains of laboratory mice, but the identity of those cells was unclear.
The mystery became a research project for biology student Clemens Ries. He tested biological markers for different brain cell types and discovered that the cells were oligodendrocyte progenitor cells, commonly called OPCs.
OPCs are young cells with an important job. They can develop into mature cells called oligodendrocytes, which make myelin, the protective coating wrapped around many nerve fibers.
Myelin works somewhat like insulation around an electrical wire. It helps electrical signals travel quickly along axons, the long extensions that nerve cells use to communicate, and it also supports the health of those fibers.
When myelin is damaged, communication between nerve cells can become slower or disrupted. This happens in diseases such as multiple sclerosis, where the immune system attacks myelin, and it can also occur after physical damage to the brain.
The researchers found that OPCs responded strongly to injury. Large numbers appeared around the edge of damaged tissue, and many later matured into oligodendrocytes capable of producing new myelin.
But the team also discovered something unexpected. About one third of the OPCs near an injury began producing corticotropin-releasing hormone, or CRH, a chemical best known for helping control the body’s response to stress.
Scientists already knew that CRH was important in the brain’s stress system. They had not known that OPCs could produce this type of signaling chemical after brain damage.
The response happened quickly. CRH production could be detected within hours after an injury, but the burst lasted only a short time and largely stopped after about three days.
That timing suggested CRH was not simply a side effect of tissue damage. Instead, it appeared to be part of the brain’s carefully controlled early response to injury.
The researchers then studied CRH receptor 1, also called CRHR1. A receptor works like a receiving station on a cell, allowing it to detect and respond to a particular chemical signal.
CRHR1 was found on another group of OPCs. When mice lacked this receptor, OPCs initially multiplied faster after injury, which might sound helpful, but the final outcome was worse.
Despite having more precursor cells early on, the mice ultimately produced fewer mature oligodendrocytes. This suggests that successful repair depends not simply on making as many OPCs as possible, but on controlling when they divide and when they mature.
CRH signaling may therefore act as a timing system. It appears to help coordinate the transition from producing new precursor cells to creating mature oligodendrocytes that can rebuild damaged myelin.
The scientists also wondered whether the same system mattered in healthy brain development. Myelin formation continues for many years after birth and is essential as brain networks mature.
In mice without CRHR1, the researchers found increased numbers of OPCs during early development. Those early differences left lasting changes in the adult brain, including thicker myelin around some of the thinner nerve fibers.
This indicates that CRH signaling may help control myelin not only after injury but also while the brain is developing. The researchers suspect that neurons could provide the CRH signal during normal development.
The work may also have implications for understanding stress and mental health. Neurons are known to release CRH during stress, and severe or long-lasting stress early in life has been associated with an increased risk of some psychiatric conditions.
Deussing and his colleagues therefore wonder whether CRH signaling in OPCs could connect stress with changes in myelin and brain development. Depression and other stress-related disorders may involve biological processes that extend beyond neurons themselves.
The research was published in the journal Cell Reports. It expands the known role of OPCs and suggests that cells traditionally viewed mainly as the source of myelin-producing cells may also participate in chemical communication after brain injury.
The findings are intriguing, but the study was conducted in mice, so it is too early to know whether the same mechanism works in exactly the same way in humans. Brain injury, multiple sclerosis, and psychiatric disorders are also highly complex and cannot be explained by one hormone or one cell type.
A major strength of the research is that it follows the CRH system across both injury and normal development. The results suggest that the timing of cell growth and maturation may be just as important as the number of repair cells present.
If future studies confirm the mechanism in humans, researchers may eventually be able to explore whether CRH signaling can be adjusted to support myelin repair. For now, the study provides a new piece of the puzzle of how the brain protects, repairs, and builds the insulation around its nerve fibers.
Source: Max Planck Institute of Psychiatry.
