Ability to handle stress, depression linked to variations in brain structure and function

October 18, 2007

Researchers at UT Southwestern Medical Center have found in mice that the ability or inability to cope with stress is linked to specific differences in the way brain cells communicate with each other.

Understanding these mechanisms – which are also present in people – may aid scientists in developing methods for humans to boost resilience to stress and depression.

"One of the major insights provided by this work is that resilience to stress is an active process," said Dr. Eric Nestler, chairman of psychiatry and senior author of the study, which appears in the Oct. 19 issue of Cell.

“This means that chronic stress, depression, post-traumatic stress disorder and similar disorders might be treated by promoting the mechanisms that underlie resilience,” said Dr. Nestler.

Mice, like humans, vary widely in their reactions to stress. Some adapt well, while others become timid and appear depressed. While stress is known to play a major role in human mental illness, scientists wonder why some people can cope well with adversity while others do not.

The researchers used male mice that had been inbred to the point that they were genetically identical. They stressed the rodents by placing them in the territory of a larger, aggressive mouse and recorded how this stress affected their ability to interact socially. In a previous study, Dr. Nestler and his colleagues established that mice which repeatedly go through this “social defeat” are a good model for human depression.

In the current study, some of the genetically identical mice interacted with the unfamiliar, more aggressive mouse, while others avoided it and showed submissive behavior.

The researchers classified the mice according to whether they had coped with the stress or not. They found that some showed a long-lasting social withdrawal, while others continued to interact normally with other mice.

The mice that coped less effectively were also less attracted to sugar but more to cocaine than the coping mice, suggesting that there was a link between their vulnerability to stress and substance abuse.

The researchers then examined two areas of the brain that are associated with pleasure and reward, called the ventral tegmental area (VTA) and the nucleus accumbens (NAc).

Neurons in the VTA send chemical signals to the NAc, and the present study shows that in mice experiencing social defeat and depression, these neurons fire faster. Upon firing, the neurons cause the release of a substance called BDNF, a nerve growth factor that the researchers have previously linked to poor coping.

The researchers further found that the vulnerable mice showed an increase in BDNF in the nucleus accumbens. The resilient ones did not, presumably because neurons from their VTAs did not fire as much. When the researchers genetically blocked BDNF in the more timid mice, they became resistant to stress.

“Preventing BDNF signaling to the nucleus accumbens may be a key mechanism of resistance to stress and depression,” Dr. Nestler said.

The researchers also found that better-coping mice had far more genes turned on and off in the VTA and NAc than vulnerable mice. This discovery suggests that successful coping with stress is an active process that involves the regulation of many genes, not just the lack of responses seen in poorly coping animals.

Three of the genes that showed the greatest difference between the two groups of mice coded for potassium channels, molecules that let potassium pass through a nerve cell’s membrane when it fires. The researchers found that the resilient animals had increased activity of the potassium channels, which counters the increased nerve firing, and hence the increase of BDNF release, in the vulnerable mice.

To explore how these results might apply to humans, the researchers obtained brain samples from depressed and non-depressed humans. The depressed people showed a 40 percent increase in BDNF levels in the nucleus accumbens, compared to controls.

From these various findings, the researchers concluded that preventing BDNF release into the nucleus accumbens may be a way to increase coping ability to stress or depression.

“It may be possible to develop compounds that improve one’s ability to cope with stress,” Dr. Nestler said. “But blocking BDNF might also affect other systems, so we must find a way to focus on this single pathway.”

Vaishnav Krishnan, an M.D./Ph.D. student in the Medical Scientist Training Program and lead author of the paper, said, “The study yields significant insights into molecular mechanisms that may underlie individual differences of people in reacting to stressful life events.”

Source: UT Southwestern Medical Center

Explore further: Cancer risk associated with key epigenetic changes occurring through normal aging process

Related Stories

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

D-galactose affects aging male and female brains differently

February 21, 2018
A study coordinated by the UAB and in collaboration with the ULL reveals the biological relevance of sex in the alteration of behaviour and the neuro-immuno-endocrine system, caused by accelerated aging with a chronic treatment ...

Healing intestinal diseases with a bacterial mix

February 16, 2018
When the bacterial ecosystem in the intestine is out of balance, there often is no other remedy than a faecal microbiota transplant. Due to the risks of this procedure, researchers from the ETH spin-off PharmaBiome are developing ...

Running helps the brain counteract negative effect of stress, study finds

February 14, 2018
Most people agree that getting a little exercise helps when dealing with stress. A new BYU study discovers exercise—particularly running—while under stress also helps protect your memory.

Identifying the dangers of chronic stress on multiple sclerosis

February 6, 2018
New research reveals how chronic stress and tiny brain inflammations cause fatal gut failure in a multiple sclerosis mouse model.

Researchers discover brain cells change following close contact with a stressed individual

February 13, 2018
Health-care workers treating soldiers with post-traumatic stress disorder (PTSD) report that some soldiers' partners and family members display symptoms of PTSD despite never serving in the military. A research study by scientists ...

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.