PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Gatekeeper of brain steroid signals boosts emotional resilience to stress

2012-04-24
(Press-News.org) PHILADELPHIA - A cellular protein called HDAC6, newly characterized as a gatekeeper of steroid biology in the brain, may provide a novel target for treating and preventing stress-linked disorders, such as depression and post-traumatic stress disorder (PTSD), according to research from the Perelman School of Medicine at the University of Pennsylvania.

Glucocorticoids are natural steroids secreted by the body during stress. A small amount of these hormones helps with normal brain function, but their excess is a precipitating factor for stress-related disorders.

Glucocorticoids exert their effects on mood by acting on receptors in the nucleus of emotion–regulating neurons, such as those producing the neurotransmitter serotonin. For years, researchers have searched for ways to prevent deleterious effects of stress by blocking glucocorticoids in neurons. However, this has proved difficult to do without simultaneously interfering with other functions of these hormones, such as the regulation of immune function and energy metabolism.

In a recent Journal of Neuroscience paper, the lab of Olivier Berton, PhD, assistant professor of Psychiatry, shows how a regulator of glucocorticoid receptors may provide a path towards resilience to stress by modulating glucocorticoid signaling in the brain. The protein HDAC6, which is particularly enriched in serotonin pathways, as well as in other mood-regulatory regions in both mice and humans, is ideally distributed in the brain to mediate the effect of glucocorticoids on mood and emotions. HDAC6 likely does this by controlling the interactions between glucocorticoid receptors and hormones in these serotonin circuits.

Experiments that first alerted Berton and colleagues to a peculiar role of HDAC6 in stress adaptation came from an approach that reproduces certain clinical features of traumatic stress and depression in mice. The animals are exposed to brief bouts of aggression from trained "bully" mice. In most aggression-exposed mice this experience leads to the development of a lasting form of social aversion that can be treated by chronic administration of antidepressants.

In contrast, a portion of mice exposed to chronic aggression consistently express spontaneous resilience to the stress and do not develop any symptoms. By comparing gene expression in the brains of spontaneously resilient and vulnerable mice, Berton and colleagues discovered that reducing HDAC6 expression is a hallmark of naturally resilient animals. While aggression also caused severe changes in the shape of serotonin neurons and their capacity to transmit electrical signals in vulnerable mice, stress-resilient mice, in contrast, escaped most of these neurobiological changes.

To better understand the link between HDAC6 and the development of stress resilience, Berton and colleagues devised a genetic approach to directly manipulate HDAC6 levels in neurons: Deletion of HDAC6 in serotonin neurons -- the densest HDAC6-expressing cell group in the mouse brain -- dramatically reduced social and anxiety symptoms in mice exposed to bullies and also fully prevented neurobiological changes due to stress, fully mimicking a resilient phenotype.

Using biochemical assays, Berton's team showed it is by promoting reversible chemical changes onto a heat shock chaperone protein, Hsp90, that HDAC6 deletion is able to literally switch off the effects of glucocorticoid hormones on social and anxiety behaviors.

Chaperones are proteins that help with the folding or unfolding and the assembly or disassembly of protein complexes. The way in which glucocorticoid receptor chaperoning and stress are linked is not well understood. Yet, genetic variations in certain components of the glucocorticoid receptor chaperone complex have been associated with the development of stress-related disorders and individual variability in therapeutic responses to antidepressants.

"We provide pharmacological and genetic evidence indicating that HDAC6 controls certain aspects of Hsp90 structure and function in the brain, and thereby modulates protein interactions, as well as hormone- and stress-induced glucocorticoid receptor signaling and behavior," explains Berton.

Together, these results identify HDAC6 as a possible stress vulnerability biomarker and point to pharmacological inhibition of HDAC6 as a potential new strategy for antidepressant interventions through regulation of Hsp90 in glucocorticoid signaling in serotonin neurons.

INFORMATION:

Co-first-authors are Julie Espallergues and Sarah L. Teegarden, along with Avin Veerakumar, Janette Boulden, Collin Challis, Jeanine Jochems, Michael Chan, Tess Petersen, Chang-Gyu Hahn, Irwin Lucki, and Sheryl G. Beck, all from Penn. Other authors are Evan Deneris, from Case Western Reserve University, Cleveland, Ohio, and Patrick Matthias, Miescher Institute for Biomedical Research, Basel, Switzerland.

This work was funded by the National Institute of Mental Health grants MH087581 and MH0754047 and grants from the International Mental Health Research Organization and the National Alliance for Research on Schizophrenia and Depression.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital - the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.

END



ELSE PRESS RELEASES FROM THIS DATE:

Atlanta Bankruptcy Attorneys Clark & Washington Note That Georgia Had 2nd Highest Bankruptcy Rate

2012-04-24
The Atlanta bankruptcy attorneys at Clark & Washington wish to inform those facing bankruptcy in Atlanta that in 2011, Georgia was the state with the second highest consumer bankruptcy filings. 2011 was a rough year for many Americans as unemployment was up and the country was mired in a recession. Atlanta was one of the major cities that was hit the hardest by the recession with an unemployment rate that was usually higher than the national average. Many Georgia families found themselves struggling under their personal debt. The top five states with the most ...

Computing the best high-resolution 3-D tissue images

Computing the best high-resolution 3-D tissue images
2012-04-24
CHAMPAIGN, Ill. — Real-time, 3-D microscopic tissue imaging could be a revolution for medical fields such as cancer diagnosis, minimally invasive surgery and ophthalmology. University of Illinois researchers have developed a technique to computationally correct for aberrations in optical tomography, bringing the future of medical imaging into focus. The computational technique could provide faster, less expensive and higher resolution tissue imaging to a broader population of users. The group describes its technique this week in the online early edition of the Proceedings ...

Laura Ashley Announces Eye-Catching Bedroom Offers

2012-04-24
Succeeding the hugely popular 50% off sofas and chairs sale, Laura Ashley, one of Britons best loved fashion and home furnishing retailers, are delighted to announce the launch of a brand new limited time offer, giving customers the chance to purchase luxury bedroom furniture and accessories at reduced prices. Bedroom Event, which is set to begin today (Tuesday 24th April), will provide customers with the perfect excuse to update the look and style of their home bedrooms, with up to 50% off gorgeous furniture and accessories. From beds, like the New Broughton Double ...

Johns Hopkins researchers uncover genes at fault for cystic fibrosis-related intestinal obstruction

2012-04-24
Researchers at Johns Hopkins have identified a gene that modifies the risk of newborns with cystic fibrosis (CF) developing neonatal intestinal obstruction, a potentially lethal complication of CF. Their findings, which appeared online March 15 in PLoS Genetics, along with the findings of their Toronto-based colleagues, published April 1 in Nature Genetics, may lead to a better understanding of how the intestines work and pave the way for identifying genes involved in secondary complications of other disorders. Soon after birth, most babies excrete their first stool, ...

GbBIS Introduces Updated Traffic Counts Aligned with NAVTEQ NAVSTREETS

GbBIS Introduces Updated Traffic Counts Aligned with NAVTEQ NAVSTREETS
2012-04-24
GbBIS, a leading resource for geography-based business information solutions, announced the introduction of its updated MPSI TrafficMetrix, aligning Traffic Counts with NAVTEQ NAVSTREETS. This realignment displays traffic markers on maps with great accuracy, producing excellent results for spatial analysis. The GbBIS update combines the extensive traffic count data from MPSI TrafficMetrix with the accuracy of NAVSTREETS. GbBIS's proprietary methodology accurately aligns traffic count markers onto NAVSTREETS, letting businesses view Traffic Counts with pinpoint accuracy. ...

The wealth of Thai villages

2012-04-24
Examining Thai villages as smaller versions of a national economy provides a new understanding of the dynamics of economic growth and yields fresh insights to the financial lives of villages and households. This is the conclusion from a new study by the Consortium on Financial Systems and Poverty. In a paper that will be published in a forthcoming issue of the journal American Economic Review, economists Archawa Paweenawat and Robert M. Townsend, describe an analytical framework that generates financial and economic accounts for villages with data drawn from household ...

Emergency room CT exams have increased in children with abdominal pain

2012-04-24
OAK BROOK, Ill. – Computed tomography (CT) utilization in pediatric patients with non-traumatic abdominal pain increased in emergency departments each year between 1999 and 2007, according to a new study published online in the journal Radiology. The study authors found no corresponding increase in ultrasound use during the same period, despite research supporting it as an important diagnostic tool for assessing pediatric abdominal pain. Non-traumatic abdominal pain is a common source of pediatric visits to the emergency department. Physicians often order CT exams when ...

Violence puts wear and tear on kids' DNA

2012-04-24
DURHAM, N.C. -- Children who have experienced violence might really be older than their years. The DNA of 10-year-olds who experienced violence in their young lives has been found to show wear and tear normally associated with aging, a Duke University study has found. "This is the first time it has been shown that our telomeres can shorten at a faster rate even at a really young age, while kids are still experiencing stress," said Idan Shalev, a post-doctoral researcher in psychology and neuroscience at the Duke Institute for Genome Sciences & Policy. Telomeres are ...

Chronic cocaine use may speed up aging of brain

2012-04-24
New research by scientists at the University of Cambridge suggests that chronic cocaine abuse accelerates the process of brain ageing. The study, published today 25 April in Molecular Psychiatry, found that age-related loss of grey matter in the brain is greater in people who are dependent on cocaine than in the healthy population. For the study, the researchers scanned the brains of 120 people with similar age, gender and verbal IQ. Half of the individuals had a dependence on cocaine while the other 60 had no history of substance abuse disorders. The researchers ...

Fewer complications, better outcomes with robot-assisted prostate cancer surgery

2012-04-24
DETROIT – Robot-assisted surgery is now both more common and far more successful than radical "open" surgery to treat prostate cancer in the United States, according to a new Henry Ford Hospital study published in the current issue of the medical journal European Urology. The research, led by scientists at Henry Ford Hospital's Vattikuti Urology Institute (VUI), is the first to compare in a nationwide population sample the results of robot-assisted radical prostatectomy (RARP) to the standard surgical procedure, open radical prostatectomy (ORP). The researchers found, ...

LAST 30 PRESS RELEASES:

Engineers uncover why tiny particles form clusters in turbulent air

GLP-1RA drugs dramatically reduce death and cardiovascular risk in psoriasis patients

Psoriasis linked to increased risk of vision-threatening eye disease, study finds

Reprogramming obesity: New drug from Italian biotech aims to treat the underlying causes of obesity

Type 2 diabetes may accelerate development of multiple chronic diseases, particularly in the early stages, UK Biobank study suggests

Resistance training may improve nerve health, slow aging process, study shows

Common and inexpensive medicine halves the risk of recurrence in patients with colorectal cancer

SwRI-built instruments to monitor, provide advanced warning of space weather events

Breakthrough advances sodium-based battery design

New targeted radiation therapy shows near-complete response in rare sarcoma patients

Does physical frailty contribute to dementia?

Soccer headers and brain health: Study finds changes within folds of the brain

Decoding plants’ language of light

UNC Greensboro study finds ticks carrying Lyme disease moving into western NC

New implant restores blood pressure balance after spinal cord injury

New York City's medical specialist advantage may be an illusion, new NYU Tandon research shows

Could a local anesthetic that doesn’t impair motor function be within reach?

1 in 8 Italian cetacean strandings show evidence of fishery interactions, with bottlenose and striped dolphins most commonly affected, according to analysis across four decades of data and more than 5

In the wild, chimpanzees likely ingest the equivalent of several alcoholic drinks every day

Warming of 2°C intensifies Arctic carbon sink but weakens Alpine sink, study finds

Bronze and Iron Age cultures in the Middle East were committed to wine production

Indian adolescents are mostly starting their periods at an earlier age than 25 years ago

Temporary medical centers in Gaza known as "Medical Points" (MPs) treat an average of 117 people daily with only about 7 staff per MP

Rates of alcohol-induced deaths among the general population nearly doubled from 1999 to 2024

PLOS One study: In adolescent lab animals exposed to cocaine, High-Intensity Interval Training boosts aversion to the drug

Scientists identify four ways our bodies respond to COVID-19 vaccines

Stronger together: A new fusion protein boosts cancer immunotherapy

Hidden brain waves as triggers for post-seizure wandering

Music training can help the brain focus

Researcher develop the first hydride ion prototype battery

[Press-News.org] Gatekeeper of brain steroid signals boosts emotional resilience to stress