Stress: Brain yields clues about why some succumb while others prevail

Oct 18, 2007

Results of a new study may one day help scientists learn how to enhance a naturally occurring mechanism in the brain that promotes resilience to psychological stress. Researchers funded by the National Institutes of Health’s National Institute of Mental Health (NIMH) found that, in a mouse model, the ability to adapt to stress is driven by a distinctly different molecular mechanism than is the tendency to be overwhelmed by stress. The researchers mapped out the mechanisms – components of which also are present in the human brain – that govern both kinds of responses.

In humans, stress can play a major role in the development of several mental illnesses, including post-traumatic stress disorder and depression. A key question in mental health research is: Why are some people resilient to stress, while others are not? This research indicates that resistance is not simply a passive absence of vulnerability mechanisms, as was previously thought; it is a biologically active process that results in specific adaptations in the brain’s response to stress.

Results of the study were published online in Cell, on October 18, by Vaishnav Krishnan, Ming-Hu Han, PhD, Eric J. Nestler, MD, PhD, and colleagues from the University of Texas Southwestern Medical Center, Harvard University, and Cornell University.

Vulnerability was measured through behaviors such as social withdrawal after stress was induced in mice by putting them in cages with bigger, more aggressive mice. Even a month after the encounter, some mice were still avoiding social interactions with other mice – an indication that stress had overwhelmed them – but most adapted and continued to interact, giving researchers the opportunity to examine the biological underpinnings of the protective adaptations.

“We now know that the mammalian brain can launch molecular machinery that promotes resilience to stress, and we know what several major components are. This is an excellent indicator that there are similar mechanisms in the human brain,” said NIMH Director Thomas R. Insel, MD.

Looking at a specific part of the brain, the researchers found differences in the rate of impulse-firing by cells that make the chemical messenger dopamine. Vulnerable mice had excessive rates of impulse-firing during stressful situations. But adaptive mice maintained normal rates of firing because of a protective mechanism – a boost in activity of channels that allow the mineral potassium to flow into the cells, dampening their firing rates.

Higher rates of impulse-firing in the vulnerable mice led to more activity of a protein called BDNF, which had been linked to vulnerability in previous studies by the same researchers. With their comparatively lower rates of impulse-firing, the resistant mice did not have this increase in BDNF activity, another factor that contributed to resistance.

The scientists found that these mechanisms occurred in the reward area of the brain, which promotes repetition of acts that ensure survival. The areas involved were the VTA (ventral tegmental area) and the NAc (nucleus accumbens).

In a series of experiments, the scientists extended their findings to provide a progressively larger picture of the vulnerability and resistance mechanisms. They used a variety of approaches to test the findings, strengthening their validity.

“The extensiveness and thoroughness of their research enabled these investigators to make a very strong case for their hypothesis,” Insel said.

For example, the researchers showed that the excess BDNF protein in vulnerable mice originated in the VTA, rather than in the NAc. Chemical signals the protein sent from the VTA to the NAc played an essential role in making the mice vulnerable. Blocking the signals with experimental compounds turned vulnerable mice into resistant mice.

The scientists also conducted a genetic experiment which showed that, in resistant mice, many more genes in the VTA than in the NAc went into action in stressful situations, compared with vulnerable mice. Gene activity governs a host of biochemical events in the brain, and the results of this experiment suggest that genes in the VTA of resilient mice are working hard to offset mechanisms that promote vulnerability.

Another component of the study revealed that mice with a naturally occurring variation in part of the gene that produces the BDNF protein are resistant to stress. The variation results in lower production of BDNF, consistent with the finding that low BDNF activity promotes resilience.

The scientists also examined brain tissue of deceased people with a history of depression, and compared it with brain tissue of mice that showed vulnerability to stress. In both cases, the researchers found higher-than-average BDNF protein in the brain’s reward areas, offering a potential biological explanation of the link between stress and depression.

“The fact that we could increase these animals’ ability to adapt to stress by blocking BDNF and its signals means that it may be possible to develop compounds that improve resilience. This is a great opportunity to explore potential ways of increasing stress-resistance in people faced with situations that might otherwise result in post-traumatic stress disorder, for example,” said Nestler.

“But it doesn’t happen in a vacuum. Blocking BDNF at certain stages in the process could perturb other systems in negative ways. The key is to identify safe ways of enhancing this protective resilience machinery,” Nestler added.

Source: National Institute of Mental Health

Explore further: Lemurs match scent of a friend to sound of her voice

add to favorites email to friend print save as pdf

Related Stories

Housing upgrade shrinks tumors in mice with cancer

Jul 08, 2010

When mice with cancer get a boost in their social life and an upgrade in living conditions, their tumors shrink, and their cancers more often go into spontaneous remission Reported in the July 9th issue of the journal Cell, these ...

Animal behavioral studies can mimic human behavior

Jan 14, 2010

Studying animals in behavioral experiments has been a cornerstone of psychological research, but whether the observations are relevant for human behavior has been unclear. Weill Cornell Medical College researchers have identified ...

Recommended for you

Lemurs match scent of a friend to sound of her voice

7 hours ago

Humans aren't alone in their ability to match a voice to a face—animals such as dogs, horses, crows and monkeys are able to recognize familiar individuals this way too, a growing body of research shows.

Chrono, the last piece of the circadian clock puzzle?

9 hours ago

All organisms, from mammals to fungi, have daily cycles controlled by a tightly regulated internal clock, called the circadian clock. The whole-body circadian clock, influenced by the exposure to light, dictates the wake-sleep ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

HarryStottle
not rated yet Oct 29, 2007
Is this some kind of test to see if we're awake? If not, why has Physorg covered the same story 3 times on the same day?
See http://www.physor...172.html
and
http://www.physor...359.html

More news stories

Low Vitamin D may not be a culprit in menopause symptoms

A new study from the Women's Health Initiative (WHI) shows no significant connection between vitamin D levels and menopause symptoms. The study was published online today in Menopause, the journal of The North American Menopa ...

Astronomers: 'Tilt-a-worlds' could harbor life

A fluctuating tilt in a planet's orbit does not preclude the possibility of life, according to new research by astronomers at the University of Washington, Utah's Weber State University and NASA. In fact, ...