Mental and physical disorders caused by chronic stress are on the rise, placing a heavy burden on society. They affect both men and women, but not necessarily in the same way. A large body of scientific evidence suggests that men and women deal with stress differently, but the causes of these differences are not yet fully understood, and in any case both men and women Combined and individualized therapies are not yet a reality.
Scientific excellence requires diversity. Research is done by both men and women, people from different backgrounds and different worldviews. The need for diversity extends to scientific experiments themselves, but even today the vast majority of life science research is conducted exclusively on male mice, which distorts the results and the ability to extrapolate from them to humans. There is a possibility.
Until the 1980s, clinical trials of new drugs were limited to men. The general view was that there was no need to include women, and that new variables such as menstruation and hormonal changes would only affect and complicate the study. For the same reason, preclinical studies have avoided the use of female animals until recently. However, there is no reason to believe that females would complicate experiments more than males, as it is known that at the molecular and behavioral level of animals, the variability between males is usually greater than between females.
A new study by researchers at the Weizmann Institute of Science in Rehovot addresses this challenge, revealing in unprecedented detail how the brains of male and female mice respond differently to stress.
How do male and female brains respond differently to stress?
In a study published in cell report Researchers from the joint laboratory of Prof. Aron Cheng at the Weizmann Institute in Munich and the Max Planck Institute for Psychiatry say that sex of stress exposure forms a cell type-specific transcriptional signature in the mouse hypothalamus. In the title, I discovered that there are subcategories of brain cells. Men and women react differently to stress. The findings may lead to a better understanding of health conditions affected by chronic stress, such as anxiety, depression, and even obesity and diabetes.
Researchers in Cheng’s lab, which specializes in studying responses to stress, suggested innovative research techniques could help change the situation. Previous studies in other laboratories have revealed specific sex differences in responses to stress, but their findings mask important differences in responses of certain cells or relatively rare It was obtained using research methods that could completely obliterate the role that cells play. By contrast, his lab uses advanced methods that allow scientists to analyze brain activity with unprecedented resolution at the level of individual cells, thus shedding new light on the differences between men and women. I can. The research team said it could pave the way for personalized treatments for these diseases.
“We turned the most sensitive research lens possible on the paraventricular nucleus (PVN) of the hypothalamus, a region of the brain that serves as the center of the stress response in mammals,” said Elena, who led the study. Dr. Brivio said. “By sequencing the RNA molecules in that part of the brain at the level of individual cells, we were able to map the stress responses of male and female mice along three main axes of how each cell type in that part of the brain responds. stress, how each cell type previously exposed to chronic stress responds to novel stress experiences, and how these responses are in men and women. does it differ from ”
Researchers have mapped gene expression in more than 35,000 individual cells, generating vast amounts of data that provide an unprecedented picture of stress responses in their range, and how men and women perceive stress. The difference in processing methods was highlighted. As part of their research, and in accordance with the principles of open access science, the researchers decided to publish the entire detailed map on a dedicated, interactive website that was launched simultaneously with the publication of the research, making it convenient for other researchers. provided information. , user-friendly access to data.
“For example, using this website, researchers focusing on a particular gene can see how that gene’s expression changes in specific cell types in response to stress, not only in women, but also in men. We will be able to see if it does,” Brivio said.
Comprehensive mapping has already allowed researchers to identify a long list of gene expression differences between men and women and between chronic and acute stress. The data showed that certain brain cells responded differently to stress in men and women. Some cells are more sensitive to stress in women, while others are more sensitive to stress in men.
The most important differences were found in a type of brain cell called an oligodendrocyte. Oligodendrocytes are a subtype of glial cells that support neurons and play an important role in regulating brain activity. In men, exposure to stress conditions, particularly chronic stress, altered not only the gene expression of these cells and their interaction with surrounding neurons, but also their structure itself. However, no major changes were observed in these cells in females, and they were not affected by exposure to stress.
“Neurons have received the most scientific attention, yet they only make up about one-third of all brain cells. Our method allows us to identify all cell types and their You can see a richer and more complete picture, including the interactions of the two,” added Dr. Juan Pablo Lopez, a former postdoctoral fellow in Cheng’s group and now head of the research department. A research group from the Department of Neuroscience at the renowned Karolinska Institutet in Sweden.
In basic research, it is still common to conduct experiments only on men. “Our findings show that it is very important to consider gender variables when it comes to stress-related health conditions, from depression to diabetes. “It has a big impact on how healthy brain cells respond to stress,” Chen explained. .
“Even if the research does not specifically focus on the differences between males and females, it is equally important to introduce the most sensitive research methods in order to obtain a complete Including female animals in behavioral science is essential,” Brivio concluded, “as much brain activity as possible needs to be imaged.”
