Experiencing several intense stress events at once, such as those during natural disasters or mass shootings, can have lasting effects on memory. New research led by the University of California, Irvine indicates that estrogen levels in the brain may contribute to this vulnerability, particularly for women. The study, published in Neuron, provides new insight into why women are more likely than men to develop post-traumatic stress disorder (PTSD) and face higher risks of dementia later in life.
The research team, led by Dr. Tallie Z. Baram, Distinguished Professor at UC Irvine’s School of Medicine, found that exposure to multiple simultaneous stressors can result in persistent memory issues and heightened responses to trauma reminders. These effects can continue for weeks or months; a single stressful event did not produce similar outcomes.
While estrogen is known for supporting learning and memory functions, the study discovered that high estrogen levels in the hippocampus—a key brain region for memory—can actually increase susceptibility to stress-related memory problems. Female mice exposed to stress during phases of their hormonal cycle with high estrogen experienced lasting memory loss and greater fear reactions to trauma reminders. Lower estrogen levels were found to be protective against these effects. Male mice also showed susceptibility due to naturally high hippocampal estrogen levels but through different biological pathways.
High estrogen was shown to alter gene activity within brain cells by loosening DNA structure (permissive chromatin), which normally aids learning and adaptation but can lead to harmful changes under extreme stress.
“High estrogen is essential for learning, memory and overall brain health,” said Baram. “But when severe stress hits, the same mechanisms that normally help the brain adapt can backfire, locking in long-lasting memory problems.”
The study also found that different types of estrogen receptors drive these effects: alpha receptors in men and beta receptors in women. Blocking these specific receptors prevented stress-related memory issues even when estrogen remained elevated, suggesting possible directions for sex-specific therapies.
“A lot of what determines vulnerability is the state your brain is already in,” said co-author Elizabeth Heller, PhD, associate professor at the University of Pennsylvania Perelman School of Medicine. “If a traumatic event hits during a period when estrogen is already unusually high, the biology can amplify the impact in lasting ways. This study shows that a state of high estrogen in a specific brain region promotes vulnerability to stress in both male and female subjects.”
Women were observed forming stronger memories related to stress more quickly than men and experienced longer-lasting impacts from trauma reminders. The timing of hormone levels during exposure—rather than after—was identified as critical for determining vulnerability.
The study was supported by the National Institutes of Health and included researchers from UC Irvine, University of Pennsylvania Perelman School of Medicine and University of British Columbia.
UC Irvine operates as a public research university within the University of California system. Established in 1965 with its campus located in Irvine, California, it offers undergraduate and graduate programs across many disciplines while focusing on advancing knowledge through research and community engagement (source). The university holds recognition for very high research activity (source) and participates actively in international collaborations (source).
For further information about UC Irvine’s academic programs or research initiatives visit the official website.