A recent study in rats suggests that high estrogen in the brain’s memory center may impair a person’s immune response to traumatic events, leading to memory problems or the tendency to develop post-traumatic stress disorder.
The research, published in April in the journal neuronDetected the effect of estrogen in the rat brain. zoomed in on sea horseA major part of the brain involved in learning and memory. Both Male and female mammals produce significant amounts of estrogen in the hippocampus, despite it often being labeled a “female” hormone.
“We’re very biased in thinking about women as high estrogen, men as low estrogen,” said the study’s co-author. elizabeth hellerAssociate Professor of Pharmacology at the Perelman School of Medicine, University of Pennsylvania. But “in this local brain area, where you have local production of estrogen, men actually sometimes have higher numbers of estrogen than women, depending on their cycling,” Heller told Live Science. Estrogen levels in the female hippocampus rise and fall in line with body-wide hormone cycles, while levels in the male hippocampus remain fairly constant.
Studies suggest that these local estrogen concentrations may influence one’s susceptibility to memory problems after large acute stress. Although this research was conducted on rats, the authors believe it is likely to have relevance to humans.
“I think it’s highly translatable,” says the study’s senior author. Dr. Tally Z. Barama professor, developmental neuroscientist and child neurologist at the University of California, Irvine told Live Science.
Estrogen isn’t always a memory enhancer
Traumatic experiences can cause memory disturbances, including difficulty remembering specific personal experiences and to be fearful reactions to previously safe, familiar situations. When these issues persist and are accompanied by deep memories of the traumatic event, they are classified as post Traumatic Stress Disorder (PTSD).
About 10% to 12% of women Women experience PTSD in their lifetime, compared to 5% to 6% of men. Some of that difference may arise from differences in the life experiences of men and women; For example, women have higher rates of sexual assault at a young age than men. Biological differences between women and men are another possible factor, but their contribution to this phenomenon is less understood.
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The new study highlights hippocampal estrogen as a difference that may matter. “The research has opened important new avenues for research on PTSD,” Victoria Luina professor emerita of psychology at Hunter College in New York City who was not involved in the work, told Live Science in an email.
In the study, researchers simulated acute traumatic events by exposing lab rats to multiple stressors at the same time, including bright lights, loud music, and the smell of other stressed rats. They tested rats through various memory tests before and after a stressful experience and compared these rodents to a group that had not experienced such stress.
Compared to unstressed rats, stressed male rats performed worse on various memory tests, and these deficits persisted for weeks. “Even after a month, his memory was still impaired — so that’s really a lasting effect,” Heller said.
Female rats and humans have similar hormone cycles, but they occur on very different time scales, with the rats’ cycles being about one seventh the length of the human cycle.
(Image credit: dra_schwartz via Getty Images)
A similar pattern was seen in female mice that were stressed during proestrus, the phase of their hormone cycle when estrogen peaks and the body prepares for ovulation. Both sets of rats learned to associate certain cues with a stressful experience and to avoid them, with the females being more sensitive to those cues than the males.
But interestingly, female mice that were stressed during estrus, when estrogen decreases and ovulation occurs, showed resilience. Their behavior and memory remained similar to that of stressed rats. “The female mice that had low levels of estrogen laughed it off — they were completely safe,” Baram said.
Studies show that hippocampal estrogen levels are similar Male and proestrous female rats, while female rats have lower levels of estrus. The researchers confirmed this using a technique called mass spectrometry, which showed that the amount of hippocampal estrogen in estrous rats was half that of males and proestrous females.
In this context, estrogen deficiency in the hippocampus appears to protect against the negative effects of stress. The finding was surprising, Baram said, because it is generally believed that estrogen boosts memory function in both sexes and declines with estrogen. As seen during menopauseAre associated with memory problems. That said, menopause occurs over a much longer period of time than the female rat’s hormone cycle, taking only four or five days.
relation to dna
Why do estrogen levels matter for memory? “Estrogen receptors directly regulate gene expression,” Heller said. By binding to its receptors, estrogen turns the activity of certain genes up or down.
Heller’s laboratory studies the mechanisms that regulate gene activity in the context of psychiatric disorders. One of those mechanisms is chromatin remodeling, which means how DNA is packaged in a cell, which can change which genes can be activated at a given time. A section of chromatin may be “open”, which exposes genes to the machinery that turns them on, or “closed”, which normally turns the genes off.
It turns out that high hippocampal estrogen in male rats and proestrous female rats opens up their chromatin in a way that makes them vulnerable to memory problems caused by severe stress. In contrast, female mice in estrus have a completely different chromatin profile that appears to be protective.
What is it about women at that stage of life that makes them more vulnerable to memory loss as they age?
Tally Z. Baram, professor, developmental neuroscientist and child neurologist at the University of California, Irvine
“We can see that the work of many of them [open] The genes are related to synapse biology, Heller said. Synapses are the points at which different neurons meet and exchange electrical signals, and they are central to the physical structure of memories in the brain.
It may be that, under most circumstances, having high levels of hippocampal estrogens is useful because they “open up” the chromatin, enabling the hippocampus to quickly form new memories in response to new experiences, Baram said. But when these experiences are accompanied by severe acute stress, “that same resiliency, the same ability of the brain to learn becomes problematic,” she said. If the results apply to humans, women may be particularly sensitive to these memory effects during certain phases of their menstrual cycles or when estrogen is high across their lifespan.
In men and women, different flavors of the estrogen receptor were responsible for stress-induced memory problems. The reasons for this difference will be the subject of future study, Baram said. Additionally, future research could try to find out where different estrogen receptors are located in the hippocampus, Heller said.
“The study provides a strong demonstration that estrogens induce sex-dependent, stress-induced changes in chromatin networks that can dramatically alter neural functions such as memory,” Luin said. Furthermore, “these results provide strong evidence that sex is a powerful biological variable.”
Historically, Female laboratory animals were excluded from the study. Because it was thought that their hormone cycles were too complex and would skew the findings. field of neuroscience exemplified this trend. In recent years, The US National Institutes of Health (NIH) requires Scientists keep gender differences in mind when designing NIH-funded human and animal studies, but progress has been made been slow on both fronts – and the current federal leadership has indicated lack of support For initiative.
It’s important to include both genders in research to understand how the brain works and responds to external factors like stress, Luin said. “An important aim of this and other studies is to protect humans from PTSD,” he said, “and this study strongly suggests that preventive treatments for PTSD may need to be tailored by gender.”
Beyond PTSD, Baram believes the research could have an impact on the risk of aging-related memory problems and dementia in women.
It is thought that the decline of estrogen at menopause increases this risk, but before menopause comes perimenopause – a period in which huge surge in estrogen. Study findings indicate that if stress appears during perimenopause, the combination of stress and high estrogen levels may contribute to memory problems. Thus, perimenopause may represent another time when women are particularly vulnerable to memory disturbances, Baram suggested.
“We have to start thinking a little differently,” he said. “What is it about women at that stage of life that makes them more vulnerable to memory loss as they age?”
This article is for informational purposes only and is not intended to provide medical advice.
This article was first published on May 4, 2026.
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