(Press-News.org) PHILADELPHIA— A new drug target to treat depression and other mood disorders may lie in a group of GABA neurons (gamma-aminobutyric acid –the neurotransmitters which inhibit other cells) shown to contribute to symptoms like social withdrawal and increased anxiety, Penn Medicine researchers report in a new study in the Journal of Neuroscience.
Experts know that people suffering from depression and other mood disorders often react to rejection or bullying by withdrawing themselves socially more than the average person who takes it in strides, yet the biological processes behind these responses have remained unclear.
Now, a preclinical study, from the lab of Olivier Berton, PhD, an assistant professor in the department of Psychiatry, in collaboration with Sheryl Beck, PhD, a professor in the department of Anesthesiology at Children's Hospital of Philadelphia, found that bullying and other social stresses triggered symptoms of depression in mice by activating GABA neurons, in a never-before-seen direct relationship between social stimuli and this neural circuitry. Activation of those neurons, they found, directly inhibited levels of serotonin, long known to play a vital role in behavioral responses—without it, a depressed person is more likely to socially withdrawal.
Conversely, when the researchers successfully put the brake on the GABA neurons, mice became more resilient to bullying and didn't avoid once -perceived threats.
"This is the first time that GABA neuron activity—found deep in the brainstem—has been shown to play a key role in the cognitive processes associated with social approach or avoidance behavior in mammals," said Dr. Berton. "The results help us to understand why current antidepressants may not work for everyone and how to make them work better—by targeting GABA neurons that put the brake on serotonin cells."
Less serotonin elicits socially defensive responses such as avoidance or submission, where enhancement—the main goal of antidepressants—induces a positive shift in the perception of socio-affective stimuli, promoting affiliation and dominance. However, current antidepressants targeting serotonin, like SSRIs, are only effective in about 50 percent of patients.
These new findings point to GABA neurons as a new, neural drug target that could help treat the other patients who don't respond to today's treatment.
For the study, "avoidant" mice were exposed to brief bouts of aggression from trained "bully" mice. By comparing gene expression in the brains of resilient and avoidant mice, Berton and colleagues discovered that bullying in avoidant mice puts GABA neurons in a state where they become more excitable and the mice exhibit signs of social defeat. Resilient mice, however, had no change in neuron levels and behavior.
To better understand the link between GABA and the development of stress resilience, Berton, Beck, and colleagues also devised an optogenetics-based approach to directly manipulate levels: Lifting GABA inhibition of serotonin neurons reduced social and anxiety symptoms in mice exposed to bullies and also fully prevented neurobiological changes due to stress.
"Our paper provides a novel cellular understanding of how social defensiveness and social withdrawal develop in mice and gives us a stepping stone to better understand the basis of similar social symptoms in humans," said Berton. "This has important implications for the understanding and treatment of mood disorders."
INFORMATION:This work was funded by the National Institute of Mental Health grants MH087581, MH0754047 and MH089800 and grants from the International Mental Health Research Organization, the National Alliance for Research on Schizophrenia and Depression and the National Institute on Drug Abuse.
Co-authors on the study include Collin Challis, Janette Boulden, Avin Veerakumar, Julie Espallergues, and R. Christopher Pierce from Penn's department of Psychiatry.
END
Research findings provide direct evidence that people with chronic diseases are more likely to be food insecure - that is suffering from inadequate, insecure access to food as a result of financial constraints. Previous research has shown that food insecurity rates are highest among low-income households, in households reliant on social assistance, reporting Aboriginal status, renting rather than owning their dwelling, and lone-parent female-led (see recent annual report from PROOF). Even taken together though, these factors provide only a partial explanation for the vulnerability ...
URBANA, Ill. – Is anyone surprised that brushes with the law are often related to finances? As one jailed man interviewed in a new University of Illinois study put it, "Most of us are in here because of money."
Incarcerated men know they will need better financial skills to succeed when they're released from prison, but most distrust the system, are more open to educators from outside their facility, and believe they need personal rather than classroom instruction, said Angela Wiley, a U of I professor of applied family studies and co-author of the article published in ...
HOUSTON -- A prominent protein activated by inflammation is the key instigator that converts glioblastoma multiforme cells to their most aggressive, untreatable form and promotes resistance to radiation therapy, an international team lead by researchers at The University of Texas MD Anderson Cancer Center reported online today in the journal Cancer Cell.
The discovery by scientists and physicians points to new ways to increase radiation effectiveness and potentially block or reverse progression of glioblastoma multiforme, the most common and lethal form of brain tumor.
"We ...
VIDEO:
Hidden for all of human history, a 460-mile-long canyon has been discovered below Greenland's ice sheet. Using radar data from NASA's Operation IceBridge and other airborne campaigns, scientists led by...
Click here for more information.
Data from a NASA airborne science mission reveals evidence of a large and previously unknown canyon hidden under a mile of Greenland ice.
The canyon has the characteristics of a winding river channel and is at least 460 miles (750 ...
Whales have been shown to increase the pigment in their skin in response to sunshine, just as we get a tan.
Research published today in Nature journal, Scientific Reports, reveals that not only do some species of whales get darker with sun exposure, incurring DNA damage in their skin just like us, they also accumulate damage to the cells in the skin as they get older.
Experts in the response of skin to UV radiation at Newcastle University, UK were called in after marine biologists in Mexico noticed an increasing number of whales in the area had blistered skin. Analysing ...
Physicists have reproduced a pattern resembling the cosmic microwave background radiation in a laboratory simulation of the big bang, using ultracold cesium atoms in a vacuum chamber at the University of Chicago.
"This is the first time an experiment like this has simulated the evolution of structure in the early universe," said Cheng Chin, professor in physics. Chin and his associates reported their feat in the Aug. 1 edition of Science Express, and it will appear soon in the print edition of Science.
Chin pursued the project with lead author Chen-Lung Hung, PhD'11, ...
Huntington's disease (HD) is a hereditary disorder characterized by the progressive onset of neurodegeneration. Children of HD patients have a 50% chance of inheriting the disease, but symptoms do not appear until middle age. While genetic testing reliably determines if children of HD sufferers are carriers of the disease, it cannot provide information as to when symptoms will appear. In this issue of the Journal of Clinical Investigation, David Eidelberg and colleagues at the Feinstein Institute of Medical Research, evaluated changes in the brain metabolism of a small ...
By carefully analyzing a 150-year-old moss bank on the Antarctic Peninsula, researchers reporting in Current Biology, a Cell Press publication, on August 29 describe an unprecedented rate of ecological change since the 1960s driven by warming temperatures.
"Whilst moss and amoebae may not be the first organisms that come to mind when considering Antarctica, they are dominant components of the year-round terrestrial ecosystem in the small ice-free zones during an austral summer," says Jessica Royles of the British Antarctic Survey and the University of Cambridge. "We ...
MAYWOOD, Il. – Researchers have identified a novel disease gene in which mutations cause rare but devastating genetic diseases known as mitochondrial disorders.
Nine rare, disease-causing mutations of the gene, FBXL4, were found in nine affected children in seven families, including three siblings from the same family. An international team of researchers report the discovery in the American Journal of Human Genetics.
The lead author is Xiaowu Gai, PhD, director of the Center for Biomedical Informatics at Loyola University Chicago Stritch School of Medicine.
Mitochondrial ...
By lowering the expression of a single gene, researchers at the National Institutes of Health have extended the average lifespan of a group of mice by about 20 percent -- the equivalent of raising the average human lifespan by 16 years, from 79 to 95. The research team targeted a gene called mTOR, which is involved in metabolism and energy balance, and may be connected with the increased lifespan associated with caloric restriction.
A detailed study of these mice revealed that gene-influenced lifespan extension did not affect every tissue and organ the same way. For example, ...
