Secret to Stress Revealed in Mice

Stress busters run the gamut from bubble baths and spiritual endeavors to anti-anxiety drugs and the bottom of a martini glass. But a new mouse study suggests the real secret to overcoming stress is hidden in the brain.

Mice, like humans, react to stressful circumstances in various ways, with some individuals snapping back to a cheery demeanor and others sinking into depression. Scientists have wondered why some people and other animals cope well and others don't.

Results of a new study, published in the Oct. 19 issue of the journal Cell, uncover chemical differences in certain brain regions of stress-resilient and stress-vulnerable mice that could explain the different adversity responses of both rodents and humans. Mice that tend to stress out produce too much of a certain chemical, apparently causing them to overreact.

The findings could point to new psychiatric drugs and other means to promote resilience in people in high-stress circumstances, including soldiers in war, disaster victims and emergency relief workers.

Depressed rodents

Researchers stressed out a group of genetically identical mice by placing each in the territory of a larger, aggressive mouse. While some of the mice interacted with the aggressive mouse, others avoided the "mean" rodent.

One month later, some of the mice were still avoiding other mice, while most had bounced back and resumed mouse mingling. The still-stressed mice had shed a significant amount of weight and showed less interest in sugar, characteristics of a depression-like state for their ilk, the scientists say.

Looking for a neural explanation, the researchers examined two brain regions associated with pleasure and reward. The neuroscientists found that dopamine neurons in the regions fired much faster in the vulnerable mice than in the resilient ones.

The swift neuron firing boosted the release of a protein called BDNF, which is thought to promote new connections between neurons. When the scientists blocked BDNF in stressed-out mice, these rodents became more resistant to stress.

“The increase in BDNF may have an adaptive role normally, allowing an animal to learn that a situation is bad and avoid it in the future,” said study leader Eric Nestler of the University of Texas Southwestern Medical Center. “But under conditions of extreme social stress, susceptible animals may be ‘over-learning’ this principle and generalizing it to other situations. They avoid their aggressors, but they also avoid all mice and even other fun things like sugar or sex.”

Happy humans

The scientists also examined brain tissues from deceased people who had a history of depression and from a group of individuals with no history of depression, finding depressed people had atypically high levels of BDNF in the brain's reward areas.

If elevated levels of the brain protein do lead to non-coping humans as it did for mice, the scientists suggest that by interfering with this protein they could also help fight stress and depression disorders.

“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," Nestler said.

However, Nestler notes that messing with one system like BDNF will likely affect other systems in ways not yet known.