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The National Institute of Mental Health awards a $344,589 grant to Associate Professor and Behavioral Neuroscientist Laura Grafe to lead research on sex differences in stress processing.

If stress is a universal feeling, why do men and women experience it differently? As the most complex organ in the human body, the brain is at the center of how stress presents in each of us, and the mechanics of how it processes stress are still being uncovered. Understanding how stress affects the brain and finding ways to manage it could improve an individual’s overall health through more tailored treatments and medications.

Associate Professor of Psychology Laura Grafe is examining this area by looking at how the sexes differ in processing stress. Grafe recently received a three-year grant totaling $344,589 from the National Institute of Mental Health (NIMH) to fund the project, “.” The study will monitor male and female rodents and the neuropeptide orexin, which plays an important role in stress and attention. Estrogen levels will also be manipulated to see how this changes orexins and cognitive flexibility after stress.

Like rodents, humans experience hormone changes that affect their behavior, adaptability, and stress levels. This research will help Grafe understand stress in the human brain and provide insights into why stress affects men and women differently.

To examine the rodents’ performance, they must participate in cognitive flexibility tasks. These tasks consist of training the rodents over a number of days to press a particular lever to receive a food reward. Rodents are trained to either discriminate between right and left levers or respond to a light cue above a lever, depending on the task. When training is complete, the rodents are tested on these tasks after undergoing a mild form of stress. �Ұ����ڱ�’s found that female rodents are better at learning the tasks, but tend to show more deficits than male rodents once stress is applied. In this new project, Grafe and her team will assess the causes of these deficits and the rodent’s abilities to change and shift when facing environmental stressors.

“This is similar to what humans experience in everyday life,” Grafe says. “We adjust to rules that are constantly changing and adapt our behavior to it.”

Grafe has dedicated much of her career to studying stress, how it affects the brain, and the particular sex differences in the context of mental health. She studied this in her postdoctoral research at the Children’s Hospital of Philadelphia, where she discovered female rodents expressed higher levels of orexins compared to male rats. This has also been reported in women compared to men in clinical populations. Grafe will continue exploring this chemical throughout her new project.

Closing the information gap between men’s and women’s healthcare is one of the motivating forces behind �Ұ����ڱ�’s research.

“Being at ��Ӱֱ��, I am driven to help this community,” Grafe says. “Understanding if there are any differences in the structure or function of the brain between sexes could translate into treatment discoveries. In the past, research has focused on male subjects, which means many drugs that are developed may not necessarily be helpful to women. I feel lucky to do my work at ��Ӱֱ�� alongside our bright young students who study psychology and neuroscience. My students gain valuable hands-on experience and are able to better understand the mechanisms underlying sex differences in this rodent work.”

If �Ұ����ڱ�’s project finds estrogen to contribute to neuropeptide activity in the brain, she plans to dive deeper into estrogen research. If not, she will pivot to understand whether other hormones contribute to stress differences between the sexes. Grafe is on sabbatical, and will teach behavioral neuroscience (PSYCB218) and a behavioral neuroscience lab (PSYCB286) next year.

Psychology