Posts tagged corticosterone
Articles and news from the latest research reports.
Biomarker Could Reveal Why Some Develop Post-Traumatic Stress Disorder
Blood expression levels of genes targeted by the stress hormones called glucocorticoids could be a physical measure, or biomarker, of risk for developing Post-Traumatic Stress Disorder (PTSD), according to a study conducted in rats by researchers at the Icahn School of Medicine at Mount Sinai and published August 11 in Proceedings of the National Academy of Sciences (PNAS). That also makes the steroid hormones’ receptor, the glucocorticoid receptor, a potential target for new drugs.
Post-Traumatic Stress Disorder (PTSD) is triggered by a terrifying event, either witnessed or experienced. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event. Not everyone who experiences trauma develops PTSD, which is why the study aimed to identify biomarkers that could better measure each person’s vulnerability to the disorder.
“Our aim was to determine which genes are differentially expressed in relation to PTSD,” said lead investigator Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. “We found that most of the genes and pathways that are different in PTSD-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD,” said Dr. Yehuda, who also heads the Mental Health Patient Care Center and PTSD Research Program at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The research team exposed a group of male and female rats to litter soiled by cat urine, a predatory scent that mimics a life-threatening situation. Most PTSD studies until now have used only male rats. Mount Sinai researchers included female rats in this study since women are more vulnerable than men to developing PTSD. The rats were then categorized based on their behavior one week after exposure to the scent. The authors also examined patterns of gene expression in the blood and in stress-responsive brain regions.
After one week of being exposed to soiled cat litter for 10 minutes, vulnerable rats exhibited higher anxiety and hyperarousal, and showed altered glucocorticoid receptor signaling in all tissues compared with resilient rats. Moreover, some rats were treated with a hormone that activates the glucocorticoid receptor called corticosterone one hour after exposure to the cat urine scent. These rats showed lower levels of anxiety and arousal one week later compared with untreated, trauma-exposed rats.
“PTSD is not just a disorder that affects the brain,” said co-investigator Nikolaos Daskalakis, MD, PhD, Associate Research Scientist in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai. “It involves the entire body, which is why identifying common regulators is key. The glucocorticoid receptor is the one common regulator that consistently stood out.”
(Image: photos.com)
Learning the smell of fear: Mothers teach babies their own fears via odor
Babies can learn what to fear in the first days of life just by smelling the odor of their distressed mothers, new research suggests. And not just “natural” fears: If a mother experienced something before pregnancy that made her fear something specific, her baby will quickly learn to fear it too — through the odor she gives off when she feels fear.
In the first direct observation of this kind of fear transmission, a team of University of Michigan Medical School and New York University studied mother rats who had learned to fear the smell of peppermint – and showed how they “taught” this fear to their babies in their first days of life through their alarm odor released during distress.
In a new paper in the Proceedings of the National Academy of Sciences, the team reports how they pinpointed the specific area of the brain where this fear transmission takes root in the earliest days of life.
Their findings in animals may help explain a phenomenon that has puzzled mental health experts for generations: how a mother’s traumatic experience can affect her children in profound ways, even when it happened long before they were born.
The researchers also hope their work will lead to better understanding of why not all children of traumatized mothers, or of mothers with major phobias, other anxiety disorders or major depression, experience the same effects.
“During the early days of an infant rat’s life, they are immune to learning information about environmental dangers. But if their mother is the source of threat information, we have shown they can learn from her and produce lasting memories,” says Jacek Debiec, M.D., Ph.D., the U-M psychiatrist and neuroscientist who led the research.
“Our research demonstrates that infants can learn from maternal expression of fear, very early in life,” he adds. “Before they can even make their own experiences, they basically acquire their mothers’ experiences. Most importantly, these maternally-transmitted memories are long-lived, whereas other types of infant learning, if not repeated, rapidly perish.”
Peering inside the fearful brain
Debiec, who treats children and mothers with anxiety and other conditions in the U-M Department of Psychiatry, notes that the research on rats allows scientists to see what’s going on inside the brain during fear transmission, in ways they could never do in humans.
He began the research during his fellowship at NYU with Regina Marie Sullivan, Ph.D., senior author of the new paper, and continues it in his new lab at U-M’s Molecular and Behavioral Neuroscience Institute.
The researchers taught female rats to fear the smell of peppermint by exposing them to mild, unpleasant electric shocks while they smelled the scent, before they were pregnant. Then after they gave birth, the team exposed the mothers to just the minty smell, without the shocks, to provoke the fear response. They also used a comparison group of female rats that didn’t fear peppermint.
They exposed the pups of both groups of mothers to the peppermint smell, under many different conditions with and without their mothers present.
Using special brain imaging, and studies of genetic activity in individual brain cells and cortisol in the blood, they zeroed in on a brain structure called the lateral amygdala as the key location for learning fears. During later life, this area is key to detecting and planning response to threats – so it makes sense that it would also be the hub for learning new fears.
But the fact that these fears could be learned in a way that lasted, during a time when the baby rat’s ability to learn any fears directly was naturally suppressed, is what makes the new findings so interesting, says Debiec.
The team even showed that the newborns could learn their mothers’ fears even when the mothers weren’t present. Just the piped-in scent of their mother reacting to the peppermint odor she feared was enough to make them fear the same thing.
Even when just the odor of the frightened mother was piped in to a chamber where baby rats were exposed to peppermint smell, the babies developed a fear of the same smell, and their blood cortisol levels rose when they smelled it.
And when the researchers gave the baby rats a substance that blocked activity in the amygdala, they failed to learn the fear of peppermint smell from their mothers. This suggests, Debiec says, that there may be ways to intervene to prevent children from learning irrational or harmful fear responses from their mothers, or reduce their impact.
From animals to humans: next steps
The new research builds on what scientists have learned over time about the fear circuitry in the brain, and what can go wrong with it. That work has helped psychiatrists develop new treatments for human patients with phobias and other anxiety disorders – for instance, exposure therapy that helps them overcome fears by gradually confronting the thing or experience that causes their fear.
In much the same way, Debiec hopes that exploring the roots of fear in infancy, and how maternal trauma can affect subsequent generations, could help human patients. While it’s too soon to know if the same odor-based effect happens between human mothers and babies, the role of a mother’s scent in calming human babies has been shown.
Debiec, who hails from Poland, recalls working with the grown children of Holocaust survivors, who experienced nightmares, avoidance instincts and even flashbacks related to traumatic experiences they never had themselves. While they would have learned about the Holocaust from their parents, this deeply ingrained fear suggests something more at work, he says.
(Source: uofmhealth.org)
Stressed-Out Tadpoles Grow Larger Tails to Escape Predators
When people or animals are thrust into threatening situations such as combat or attack by a predator, stress hormones are released to help prepare the organism to defend itself or to rapidly escape from danger—the so-called fight-or-flight response.
Now University of Michigan researchers have demonstrated for the first time that stress hormones are also responsible for altering the body shape of developing animals, in this case the humble tadpole, so they are better equipped to survive predator attacks.
Through a series of experiments conducted at field sites and in the laboratory, U-M researchers demonstrated that prolonged exposure to a stress hormone enabled tadpoles to increase the size of their tails, which improved their ability to avoid lethal predator attacks.
"This is the first clear demonstration that a stress hormone produced by the animal can actually cause a morphological change, a change in body shape, that improves their survival in the presence of lethal predators. It’s a survival response," said Robert Denver, a professor of molecular, cellular and developmental biology and of ecology and evolutionary biology.
The team’s surprising findings are detailed in a paper to be published online March 5 in the journal Proceedings of the Royal Society B. First author of the paper is Jessica Middlemis Maher, a former U-M doctoral student, now at Michigan State University, who conducted the work for her dissertation.
Scientists have long known that environmental changes can prompt animals and plants to alter their morphology and physiology, as well as the timing of developmental events. For example, tadpoles can accelerate metamorphosis into frogs in response to a drying pond, a high density of predators or a lack of food.
The term “phenotypic plasticity” is used to describe modifications by animals and plants in response to a changing environment.
"There’s been a lot of interest in phenotypic plasticity among developmental biologists and evolutionary ecologists for more than 70 years, but there’s been relatively little focus on the mechanisms by which the environmental signal is translated into a functional response," Denver said.
"We’ve known, for example, that tadpoles can change their body shape in response to predation risk. But until now, nobody knew the basic physiological mechanisms mediating that response. That’s what’s novel about this study."
(Image: Wikimedia Commons)
Repeated aggressions trigger social aversion in mice
One of the mechanisms involved in the onset of stress-induced depression has been highlighted in mice by researchers from CNRS, Inserm and UPMC. They have determined the role of the corticosterone (stress hormone) receptor, in the long-term behavioral change triggered by chronic stress. In mice subject to repeated aggressions, this receptor participates in the development of social aversion by controlling the release of dopamine, a key chemical messenger. If this receptor is blocked, the animals become “resilient”: although anxious, they overcome the trauma and no longer avoid contact with their fellow creatures. This work is published in Science on 18 January 2013.