Do the sexes differ in their response to stress? Converging evidence suggests that at least in some cases they do, according to recent findings by research supported in part by a 2013 NARSAD Young Investigator Grant to Ilia N. Karatsoreos, Ph.D., of Washington State University. Working together with former NARSAD Grantee and Scientific Council member Bruce S. McEwen, Ph.D., of The Rockefeller University, and an inter-institutional team, the researchers reported in the May issue of Molecular Psychiatry that the female sex hormone estrogen protected laboratory animals against some of the detrimental effects of stress.

The research team, led by former NARSAD Grantee Zhen Yan, Ph.D., along with Eunice Y. Yuen Ph.D., both of the State University of New York, Buffalo, specifically found that estrogen played a protective role on glutamatergic transmission and cognition. The glutamatergic system regulates glutamate, the most important excitatory neurotransmitter in the brain. In the study, young female rats exposed to a week of repeated restraint stress showed no negative effects on what is called temporal order recognition memory (TORM), a cognitive process controlled by the prefrontal cortex (PFC), a brain area where higher thinking occurs. Impairment in TORM was observed in stressed male rats.

When the researchers blocked estrogen in the stressed female animals, they then showed the same negative effects as the males. Conversely, detrimental effects were prevented in males that were administered estrogen. The authors suggest, therefore, that the protective effects estrogen appears to provide on glutamatergic transmission and PFC-dependent cognition and memory may underlie the apparent stress resilience of females.

Read an abstract of the research paper.