A degree of stress is a normal part of life, but stress can become problematic in vulnerable individuals and contribute to the development of mental illnesses such as anxiety and depression. New research by a team including Brain & Behavior Research Foundation NARSAD Grantees Zhen Yan, Ph.D. and Eunice Y. Yuen, Ph.D., of the University of Buffalo and Bruce S. McEwen, Ph.D., of Rockefeller University (also a Foundation Scientific Council Member) suggests that through a protective effect of estrogen in the brain, resilience to chronic stress is amplified in women. The research findings were published online on July 9, 2013 in Molecular Psychiatry.

 

“We have examined the molecular mechanism underlying gender-specific effects of stress,” says study senior author Zhen Yan, Ph.D., Professor, Department of Physiology and Biophysics, University of Buffalo School of Medicine and Biomedical Sciences. “Previous studies have found that females are more resilient to chronic stress, and now our research has found the reason why.”

 

The researchers mimicked a situation of “being under pressure” in their study with rats. They found that young female rats, after one week of exposure to stress, showed no impairment in their ability to remember and recognize objects they had previously been shown but the young males exposed to the same stress did. This impairment in short-term memory signifies a malfunction in the signaling of the glutamate receptor in the prefrontal cortex, the brain region that controls working memory, attention, decision-making, emotion and other high-level “executive” processes. The same research team showed last year (in a paper in Neuron) that repeated stress resulted in loss of the glutamate receptor in the prefrontal cortex of young males. This current paper shows that the glutamate receptor in the prefrontal cortex of stressed females is intact, thus providing further support for a growing body of research demonstrating that the glutamate receptor is the molecular target of stress, mediating the stress response.

 

“When estrogen signaling in the brains of females was blocked, stress exhibited detrimental effects on them,” explains Dr. Yan. “When estrogen signaling was activated in males, the detrimental effects of stress were blocked. We still found the protective effect of estrogen in female rats whose ovaries were removed. It suggests that it might be estrogen produced in the brain that protects against the detrimental effects of stress.”

 

The findings suggest a new avenue for development of medication treatments for stress. “If we could find compounds similar to estrogen that could be administered without causing hormonal side effects, they could prove to be a very effective treatment for stress-related problems in males,” concludes Dr. Yan.