Mental and physical disorders caused by chronic stress are constantly on the rise, putting a significant strain on society. They affect both men and women, but not necessarily in the same way. A new study at Weizmann reveals in unprecedented detail how the brains of males and females respond differently to stress.
Researchers from Prof. Alon Chen’s joint laboratory at Weizmann and the Max Planck Institute of Psychiatry in Munich discovered that a subcategory of brain cells responds to stress in a totally different manner in males and females. The findings could lead to a better understanding of health conditions affected by chronic stress, such as anxiety, depression, and even obesity and diabetes. The continued work of scientists at Weizmann could also pave the way toward personalized therapies for these disorders in men and women.
Previous studies in other labs had uncovered certain sex differences in the response to stress, but those findings were obtained using research methods that could mask significant differences in the responses of specific cells or even entirely erase the roles played by relatively rare cells. Prof. Chen’s laboratory, in contrast, uses advanced methods that allow scientists to analyze brain activity at an unprecedented resolution, shedding new light on the differences between the sexes.
“We turned the most sensitive research lens possible onto the area of the brain that acts as a central hub of the stress response,” says Dr. Elena Brivio, who led the study. “By sequencing the RNA molecules in that part of the brain on the level of the individual cell, we were able to map the stress response in males and females along three main axes: how each cell type in that part of the brain responds to stress, how each cell type previously exposed to chronic stress responds to a new stress experience, and how these responses differ between males and females.”
The study proved unprecedented in both its scope and in highlighting the differences between how males and females perceive and process stress. Researchers mapped out gene expression in more than 35,000 individual cells. The comprehensive mapping has already allowed the researchers to identify a long list of differences between males and females, and between chronic and acute stress.
The most significant difference was found in a type of brain cell called the oligodendrocyte – a subtype of glial cell that provides support to nerve cells and plays an important role in regulating brain activity. In males, exposure to stress conditions, especially chronic stress, changed not only the gene expression in these cells and their interactions with surrounding nerve cells but also their very structure. In females, however, no significant change was observed in these cells, and they were not susceptible to stress exposure.
“Our findings show that, when it comes to stress-related health conditions, from depression to diabetes, it’s very important to take the sex variable into account, since it has a significant impact on how different brain cells respond to stress,” Prof. Chen explains. “Even if a study does not specifically focus on the differences between males and females, it’s essential ... especially in neuroscience and behavioral science ... in order to obtain as complete a picture of brain activity as possible,” Dr. Brivio adds.
