Nav: Home

How estrogen modulates fear learning

January 18, 2017

Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD) at some points in their menstrual cycles or lifetimes, while high estrogen levels may be protective.

New research from Emory University School of Medicine and Harvard Medical School provides insight into how estrogen changes gene activity in the brain to achieve its protective effects.

The findings, published in Molecular Psychiatry, could inform the design of preventive treatments aimed at reducing the risk of PTSD after someone is traumatized.

The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification of DNA that is usually a sign of genes that are turned off.

The group included adult women of child-bearing age, in which estrogen rises and falls with the menstrual cycle, and women that had gone through menopause and had much lower estrogen levels.

"We knew that estrogen affects the activity of many genes throughout the genome," says Alicia Smith, PhD, associate professor and vice chair of research in the Department of Gynecology and Obstetrics at Emory University School of Medicine. "But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out."

That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in "resting state" brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning.

On top of that, experiments with female mice showed that the HDAC4 gene was activated in the amygdala while the mice were undergoing fear learning, but only when estrogen levels in the mice were low.

Smith says these results could lead to estrogen being used as a preventive treatment to lower the risk of PTSD after trauma. More information about how estrogen exerts its effects is coming to light; the authors note that in addition to modulating fear learning, estrogen has also been proposed to alter pain perception.

In this paper, estrogen's effects in males were not studied; other scientists have found that in males, testosterone is converted into estrogen in the brain, where it plays a key role in development.
-end-
The paper was a collaboration with Kerry Ressler, MD, PhD, previously at Emory and Yerkes National Primate Research Center and now at Harvard's McLean Hospital, and Tanja Jovanovic, PhD and her team from Emory's Department of Psychiatry and Behavioral Sciences. The first author of the paper is Stephanie Maddox, PhD, a post-doctoral researcher working with Ressler.

The research was supported by the National Institute of Mental Health (MH071537, MH096764, MH085806), the Brain & Behavior Research Foundation, the Howard Hughes Medical Institute, the Behrens-Weise Foundation and the NIH's Office of Research Infrastructure Programs (Primate centers: P51OD011132).

Emory Health Sciences

Related Estrogen Articles:

How estrogen modulates fear learning
Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD), while high estrogen levels may be protective.
Estrogen signaling impacted immune response in cancer
New research from The Wistar Institute showed that estrogen signaling was responsible for immunosuppressive effects in the tumor microenvironment across cancer types.
Are drops in estrogen levels more rapid in women with migraine?
Researchers have long known that sex hormones such as estrogen play a role in migraine.
Estrogen-deficient female athletes' memory improves with estrogen
In young female athletes who stop having their menstrual periods because of excessive exercise, estrogen replacement appears to improve their memory, a new study finds.
Blood clot risk lower for estrogen-only, transdermal, and vaginal estrogen at menopause
A Swedish population study is helping answer lingering questions about hormone therapy safety.
U of G researchers study tie between estrogen, memory
A new study by University of Guelph researchers that narrows down where and how estrogens affect the brain may help in understanding how the hormones affect cognition and memory in women.
New sensor sends electronic signal when estrogen is detected
Researchers in New Zealand have developed a new sensor that can detect low levels of E2, one of the primary estrogen hormones, in liquids.
Estrogen drug may not benefit women with Alzheimer's dementia
An estrogen-like drug, raloxifene, has no demonstrated benefit on memory and thinking skills for women with dementia due to Alzheimer's disease, according to a study published in the Nov.
Panel recommends improvements in estrogen testing accuracy
Unreliable estrogen measurements have had a negative impact on the treatment of and research into many hormone-related cancers and chronic conditions.
Interaction of estrogen receptor and coactivators seen for first time
In a recent study with Dr. Wah Chiu, professor of biochemistry and molecular biology at Baylor, O'Malley for the first time visualized the 900 kiloDalton molecular machine made up of the receptor, its coactivator SRC-3, another coactivator called p300, and the DNA that it controls, through the use of an electron cryo-microscope and advanced computational analysis.

Related Estrogen Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".