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

Hyperactive nerve cells may contribute to depression

Identification of cellular mechanism may lead to novel and effective treatments

2011-02-24
(Press-News.org) UPTON, NY - Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, Cold Spring Harbor Laboratory, and the University of California, San Diego School of Medicine, have identified hyperactive cells in a tiny brain structure that may play an important role in depression. The study, conducted in rats and appearing in the February 24, 2011, issue of Nature, is helping to reveal a cellular mechanism for depressive disorders that could lead to new, effective treatments.

The research provides evidence that inhibition of this particular brain region - the lateral habenula - using implanted electrodes can reverse certain behaviors associated with depression, and also provides a mechanism to explain this effect. These findings lend support to the use of deep brain stimulation as a clinical treatment for people with long-standing, treatment-resistant depression.

"This research identifies a new anatomical circuit in the brain that mediates depression, and shows how it interacts with the brain's reward system to trigger a constant disappointment signal - which certainly would be depressing," said Fritz Henn, a neurobiologist and psychiatrist at Brookhaven and Cold Spring Harbor laboratories and a co-investigator on the research. "But," he added, optimistically, "identifying this circuit and how it works may open new doors to reversing these effects."

For example, said co-investigator Roberto Malinow, a professor of neurosciences at the UCSD School of Medicine, "it's possible that the genes specifically expressed in these neurons could be targeted genetically or pharmacologically in order to manipulate them and reduce depression."

Scientists have known that cells in the lateral habenula are activated by negative or unpleasant events, including punishment and disappointment, such as when you don't get an expected reward. It may seem intuitive that such negative stimuli can lead to depression, but not everyone who experiences disappointment collapses into a state of helplessness. To explore this connection, the scientists wanted to take a closer look at the brain circuits.

They examined the sensitivity of lateral habenula brain cells - particularly those that connect and send signals to the brain's reward centers - in two animal models of "learned helplessness," a form of depression, as well as in control animals that weren't helpless.

Overall, the scientists found that these lateral habenula nerve cells were hyperactive in the depressed animals but not in the controls. Furthermore, the degree of hyperactivity coincided with the degree of helplessness.

"The activation of the lateral habenula is known to influence the release of serotonin and norepinepherine, two targets of current antidepressant medications," said Henn. "The current study looked at the role of the lateral habenula in terms of the dopamine system, the system involved in reward signaling. We found that hyperactivity in the lateral habenula due to stress-induced helplessness shuts off the brain's reward system."

To explore whether electrical stimulation could potentially reverse this reward-dampening effect, the researchers placed a stimulating electrode in the lateral habenula and measured the effects on the brain cells leading to the reward center. This was a study of rat brain cells that simulated the effects of deep brain stimulation, a technique that is currently being explored as a treatment for clinical depression, which has shown promising results. The scientists found that electrical stimulation of hyperactive habenula brain cells markedly decreased excitatory activity leading to the reward center.

Next the scientists tested to see if deep brain stimulation in living rats that exhibited helplessness would affect their behavior. The result was a marked reduction in helpless behavior that was dependent on both placement of the electrode in the lateral habenula (not adjacent brain regions), and the intensity of the stimulation.

"Our results clearly show that suppression of synaptic transmission at the lateral habenula through deep brain stimulation can acutely reverse helpless behavior in rats," said Henn. "It's very likely that this beneficial effect was mediated by a suppression of excitatory nerve cells leading to the brain's reward system, as we observed in the cellular studies."

"Our study provides a cellular mechanism that may explain the hyperactivity of lateral habenula nerve cells observed in depressed humans and animal models of depression, as well as why 'silencing' these circuits, whether surgically or pharmacologically, can reduce depression-like symptoms in animals," Henn said.

Identifying these specific brain circuits and their dysfunction in depression may open the door to new effective treatments, including, potentially, lateral-habenula-targeted deep brain stimulation.

### This research was supported through Laboratory Directed Research and Development funding at Brookhaven Lab, and by the Simons Foundation, the Dana Foundation, the National Institute of Mental Health, and a Shiley-Marcos endowment at UCSD.

In addition to Henn and Malinow, co-authors include: Bo Li (UCSD and Cold Spring Harbor), Joaquin Piriz (UCSD), Martine Mirrione (Cold Spring Harbor and Brookhaven), Chihye Chung (UCSD), Christophe Proulx (UCSD), and Daniela Schulz (Brookhaven).

All research involving laboratory animals at Brookhaven National Laboratory is conducted under the jurisdiction of the Lab's Institutional Animal Care and Use Committee (IACUC, http://www.bnl.gov/ora/IACUC.asp) in compliance with the Public Heath Service (PHS) Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/phspol.htm), the U.S. Department of Agriculture's Animal Welfare Act (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), and the National Academy of Sciences' Guide for the Care and Use of Laboratory Animals (http://www.nap.edu/readingroom/books/labrats/). This research has enhanced understanding of a wide array of human medical conditions including cancer, drug addiction, Alzheimer's and Parkinson's diseases, and normal aging and has led to the development of several promising treatment strategies.

Related Links

Scientific paper (available Wednesday, February 23, 2011, after 1 p.m. U.S. Eastern Time): Synaptic potentiation onto habenula neurons in the learned helplessness model of depression: http://www.nature.com/nature/journal/v470/n7334/full/nature09742.html

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more at http://www.bnl.gov/newsroom , or follow Brookhaven Lab on Twitter, http://twitter.com/BrookhavenLab .


ELSE PRESS RELEASES FROM THIS DATE:

Aging, interrupted

Aging, interrupted
2011-02-24
VIDEO: Salk scientist Dr. Belmonte discusses the research. Click here for more information. LA JOLLA, CA—The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because lifespans of eight decades or more make it difficult to study. Now, researchers at the Salk Institute for Biological Studies have replicated premature aging in the lab, allowing them to study aging-related disease in a dish. In ...

New biological pathway identified for post-traumatic stress disorder

2011-02-24
High blood levels of a hormone produced in response to stress are linked to post-traumatic stress disorder in women but not men, a study from researchers at Emory University and the University of Vermont has found. The results are scheduled for publication in the Feb. 24 issue of Nature. The hormone, called PACAP (pituitary adenylate cyclase-activating polypeptide), is known to act throughout the body and the brain, modulating central nervous system activity, metabolism, blood pressure, pain sensitivity and immune function. The identification of PACAP as an indicator ...

New 'thunder-thighs' dinosaur discovered

2011-02-24
LONDON – A new dinosaur named Brontomerus mcintoshi, or "thunder-thighs" after its enormously powerful thigh muscles, has been discovered in Utah, USA. The new species is described in a paper recently published in the journal Acta Palaeontologica Polonica by an international team of scientists from the U.K. and the U.S. A member of the long-necked sauropod group of dinosaurs which includes Diplodocus and Brachiosaurus, Brontomerus may have used its powerful thighs as a weapon to kick predators, or to help travel over rough, hilly terrain. Brontomerus lived about 110 ...

Quantum hot potato: NIST researchers entice 2 atoms to swap smallest energy units

Quantum hot potato: NIST researchers entice 2 atoms to swap smallest energy units
2011-02-24
BOULDER, Colo.—Physicists at the National Institute of Standards and Technology (NIST) have for the first time coaxed two atoms in separate locations to take turns jiggling back and forth while swapping the smallest measurable units of energy. By directly linking the motions of two physically separated atoms, the technique has the potential to simplify information processing in future quantum computers and simulations. Described in a paper published Feb. 23 by Nature,* the NIST experiments enticed two beryllium ions (electrically charged atoms) to take turns ...

Virus-mimicking nanoparticles can stimulate long lasting immunity

2011-02-24
Vaccine scientists say their “Holy Grail” is to stimulate immunity that lasts for a lifetime. Live viral vaccines such as the smallpox or yellow fever vaccines provide immune protection that lasts several decades, but despite their success, scientists have remained in the dark as to how they induce such long lasting immunity. Scientists at the Emory Vaccine Center have designed tiny nanoparticles that resemble viruses in size and immunological composition and that induce lifelong immunity in mice. They designed the particles to mimic the immune‑stimulating effects ...

Quantum computer -- tune in now

Quantum computer -- tune in now
2011-02-24
The Austrian research group led by physicist Rainer Blatt suggests a fundamentally novel architecture for quantum computation. They have experimentally demonstrated quantum antennae, which enable the exchange of quantum information between two separate memory cells located on a computer chip. This offers new opportunities to build practical quantum computers. The researchers have published their work in the scientific journal Nature. Six years ago scientists at the University of Innsbruck realized the first quantum byte – a quantum computer with eight entangled quantum ...

Microbes help children to breathe easily

2011-02-24
The incidence of asthma among children in Europe continues to rise. But not all children are equally at risk. Several studies published over the past few years have shown that children living on farms are significantly less likely to develop asthma than others. An international team of researchers including Dr. Markus Ege and Professor Erika von Mutius of Children's Surgical Clinic in the Dr. von Hauner Children's Hospital (Medical Center of the University of Munich) has just published an epidemiological study that confirms this finding. It shows that the lower susceptibility ...

Quantum simulator becomes accessible to the world

Quantum simulator becomes accessible to the world
2011-02-24
Experimental physicists have put a lot of effort in isolating sensitive measurements from the disruptive influences of the environment. In an international first, Austrian quantum physicists have realized a toolbox of elementary building blocks for an open-system quantum simulator, where a controlled coupling to an environment is used in a beneficial way. This offers novel prospects for studying the behavior of highly complex quantum systems. The researchers have published their work in the scientific journal Nature. Many phenomena in our world are based on the nature ...

Before the explosion -- volcano's warning tremors explained

Before the explosion -- volcanos warning tremors explained
2011-02-24
New Haven, Ct. - No matter their size or shape, explosive volcanoes produce tremors at similar frequencies for minutes, days or weeks before they erupt. In the Feb. 24 issue of the journal Nature, researchers at Yale University and the University of British Columbia (UBC) describe a model that explains this strange phenomenon – and may help forecast deadly eruptions. When such volcanoes erupt they can shoot hot ash up to 40 kilometers into the atmosphere and cause devastating destruction when the ash column collapses and spreads as "pyroclastic flows." Prior to most ...

Researchers use genomics to investigate TB outbreak

2011-02-24
Vancouver, BC - Scientists supported by Genome BC have set a new standard for studying outbreaks of infectious disease by combining advanced genomics with a detailed map of the social relationships between cases to investigate a recent outbreak of tuberculosis in a BC community. The study tracked 41 individuals who developed tuberculosis: patient interviews revealed a tightly-knit community where most patients knew one another, while DNA fingerprinting of the bacterial samples from each individual showed them to be identical to each other. These two factors together ...

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] Hyperactive nerve cells may contribute to depression
Identification of cellular mechanism may lead to novel and effective treatments