Experiencing chronic stress day after day can produce wear and tear on the body physically and mentally, and can have a detrimental effect on learning and emotion. However, acute stress - a short stressful incident - may enhance learning and memory.

Researchers at the University at Buffalo have shown, in trials using rodents as an animal model, that acute stress can produce a beneficial effect on learning and memory, through the effect of the stress hormone corticosterone (cortisol in humans) on the brain’s prefrontal cortex, a key region that controls learning and emotion.

Specifically, they demonstrated that acute stress increases transmission of the neurotransmitter glutamate and improves working memory.

“Stress hormones have both protective and damaging effects on the body,” said Zhen Yan, professor of physiology and biophysics at UB and senior author on the study. “This paper and others we have in the pipeline explain why we need stress to perform better, but don’t want to be stressed out.”

The study appeared July 20 in the online edition of Proceedings of the National Academy of Sciences and will be published in an upcoming print version of the journal. Eunice Y. Yuen, Ph.D., UB research assistant professor of physiology and biophysics, is the first author on the study.

To test the effect of acute stress on working memory, Yan, Yuen and colleagues trained rats in a maze until they could complete it correctly 60-70 percent of the time. When the rodents reached this level of accuracy for two consecutive days, half were put through a 20-minute forced swim, which served as acute stress, and then were put through the maze again.

Results showed that the stressed rats made significantly fewer mistakes as they went through the maze both four hours after the stressful experience and one day post-stress, compared to the non-stressed rats.

To determine if the corticosterone neuropathway was responsible for the improved memory, as they proposed, researchers injected one group of rats before the stressful forced-swim with a medicinal compound that blocks the pathway, and injected another group with saline. Results showed that the saline group, in which the corticosterone neuropathway was not blocked, performed better in the maze than the blocked group.

The researchers also determined that the stressful experience did not increase depression or anxiety-related behavior in the animals.

“It is known that stress has both positive and negative actions in the brain, but the underlying mechanism is elusive,” said Yan. “Several key brain regions involved in cognition and emotions, including the prefrontal cortex, have been identified as the primary target of corticosteroid, the major stress hormone.

“Our current study identifies a novel mechanism that underlies the impact of acute stress on working memory, a cognitive process depending on glutamate receptor-mediated excitatory signals in prefrontal cortex circuits.”

The investigators have expanded this research in several directions. In a paper currently under review, they have identified the key signaling molecules that link acute stress to the enhancement of glutamate receptors and working memory.

“In addition,” noted Yan, “we have discovered that chronic stress suppresses the transmission of glutamate in the prefrontal cortex of male rodents, which is opposite to the facilitating effect of acute stress, and that estrogen receptors in female rodents make them more resilient to chronic stress than male rats.

“All these studies should bring new insights into the complex actions of stress in different circumstances that may be applicable to humans in the future,” she said.

Wenhua Liu, Ph.D., postdoctoral associate, and Jain Feng, Ph.D., associate professor, both in the UB Department of Physiology and Biophysics, are co-authors on the study, along with Ilia N. Karatsoreos, Ph.D., and Bruce S. McEwen, Ph.D., from The Rockefeller University.

The research was supported by grants from the National Institutes of Health to Yan and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award to Yuen.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB’s more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

Lois Baker
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