Turn gray overnight?
Painful injections caused mice to turn gray from stress
Polina Loseva, N+1
The phenomenon of accelerated graying from stress is caused by the loss of stem cells in the hair follicles. This conclusion was reached by scientists who injected mice with the toxin and monitored the condition of their skin. They found that under the influence of stress, the precursor cells of melanocytes disappear from the follicles, and norepinephrine serves as an intermediary in this process. The work was published in the journal Nature (Zhang et al., Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells).
In literature, there are often stories that some character "turned gray overnight." So, for example, they told about the Empress Marie Antoinette, who allegedly turned gray after her escape failed during the French Revolution. Despite the fact that these stories do not always look plausible, doctors have indeed described the phenomenon of accelerated graying in people several times (aka Marie Antoinette syndrome).
The reason for such a sharp graying is usually called stress, but it is still unclear exactly how it affects the hair. It can be assumed, for example, that the matter is in the cells-melanocytes, which give color to hair. They are formed next to the hair follicle from the corresponding stem cells. Under the influence of stress, melanocytes themselves, their progenitor cells, or only the pigment melanin can be destroyed.
Bing Zhang from Harvard University and his colleagues decided to look into this issue because they are interested in tissue regeneration and how it changes under stress. The researchers worked with black laboratory mice. In order to choose the optimal stress conditions for graying, three groups of mice were put in different stressful situations.
The first group was immobilized: the animals were placed in a cramped cage for several hours or several days. The second group was affected by chronic unpredictable stress: cell swinging, sudden change of illumination, transplanting from cell to cell, immobilization, and so on. The third group got physiological stress: animals were injected with resiniferatoxin — an analogue of capsaicin from hot pepper. Then the mice were shaved bald to speed up hair growth, and calculated on what percentage of the total area gray hair would grow. The most effective way to cause graying was the last one: after injections, almost 30 percent of the animals' skin was covered with gray hair. However, it did not happen for one night, as they say in the books, and in a couple of weeks — that's how long it takes to change one generation of hair in mice.
An infographic showing how stem cells are depleted in response to stress, causing mouse fur to turn gray.
Scientists have verified that under the influence of the toxin, mice really experienced physiological stress: the concentration of corticosterone in their blood increased three times, and norepinephrine — a dozen times. Then they confirmed that stress and graying were caused by the toxin: they injected mice with an analgesic and found that the hormone levels did not differ from the control group (which did not receive the toxin), and gray hair covered only a few percent of the skin (compared to 30 percent — without an analgesic).
To find out which cells are affected by stress, scientists injected the toxin into animals in the late stages of follicle growth. At this moment, mature melanocytes have already formed in the hair, and stem cells are located separately — in a pouch next to the follicle. After the injection of the toxin, mature melanocytes continued to produce melanin, but there were five times fewer stem cells. Thus, scientists have found that stress does not affect the "finished" hair, but only the production of new pigmented cells.
At the next stage of the work, the researchers were looking for an intermediary between stress and stem cells. Such could be, for example, immune cells — however, mutant mice, deprived of various elements of the immune system, turned gray in the same way as ordinary animals. Corticosterone and norepinephrine could also act as an intermediary. However, an artificial increase in the level of corticosterone did not make the animals turn gray, unlike norepinephrine: when it was injected into the animals under the skin, even in the absence of painful injections, the hair lost pigmentation at the injection sites.
Norepinephrine can enter tissues from two sources. The first is the adrenal glands, the second is the sympathetic nerve fibers. When scientists injected the toxin into mice with removed adrenal glands, the animals still turned gray. Therefore, the researchers suggested that the hair follicles "learn" about stress from the sympathetic nervous system. And indeed: when animals were injected with a neurotoxin that destroys sympathetic fibers, they stopped turning gray in response to pain stress.
Finally, the researchers found out what happens to stem cells in response to stress. After coloring the hair follicles of animals that received a painful injection, they noticed that there were no traces of stem cell death or DNA damage in their nucleus on the preparations. On the contrary, the cells were actively dividing or moving.
Based on the results of the experiments, the authors of the work built the following chain of events: when a stress factor acts on the body, sympathetic nerve fibers react to it. They secrete norepinephrine, which causes the stem cells, the precursors of melanocytes, to divide and migrate. Apparently, this is the reason for the loss of pigmentation: normally, stem cells should be located in a certain place of the follicle and rarely multiply. When they divide too often, their resources are depleted, and during migration they often leave the follicle, and as a result they cannot replenish the supply of melanocytes. The authors note that in the future it would be interesting to check whether these processes are involved in the "planned", age-related loss of hair pigmentation.
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