DEPRESSION
April 25, 2014

Boosting the Brain's Resilience

Mice prone to depression-like behaviors became resistant to stress and depression after a jump-start.

Just like some people, when certain mice are exposed to stress, they begin to exhibit depressive behaviors — they become withdrawn, anxious and listless. And just like other people, some mice seem to be protected from depression, even when exposed to stressful circumstances.

That's why the finding of a new study — that mice can be “jump started“ into a resilient state where they are no longer prone to depression — is so exciting.

In mice, out-of-balance electrical activity within the brain’s reward circuitry has been linked to depression. “Resilient” mice show much more stable electrical activity within these same brain regions.

When researchers from the Icahn School of Medicine at Mount Sinai looked more closely at the unstable electrical activity in the brains of depressed mice, they discovered something quite surprising. By boosting the type of runaway electrical activity associated with depressive behaviors, they actually ended up triggering a stabilized response.

Even better, once electrical balance was restored, previously susceptible animals were no longer prone to becoming withdrawn, anxious, and listless following socially stressful experiences.

Once stable, these mice were less likely to develop depressive behaviors following stress.

This counterintuitive self-stabilizing response appears to promote resilience, and the discovery may pave the way for new types of antidepressants.

“As we get to the bottom of a mystery that has perplexed the field for more than a decade, the story takes an unexpected twist that may hold clues to future antidepressants that would act through this counterintuitive resilience mechanism,” Thomas R. Insel, M.D., Director of the National Institute of Mental Health, said in a statement.

As seen in previous studies of mice susceptible to depression, neurons in the brain’s reward circuit affected by the neurotransmitter dopamine showed excessive electrical activity.

What did surprise the researchers, however, was that stress-resilient mice showed this same electrical over-excitation; and in fact, it was actually stronger than in mice vulnerable to depressed behavior. But the resilient mice also showed a simultaneous increase in inhibitory currents, which reduced or balanced out the over-excitation. Potassium was the chemical messenger responsible for inhibiting effect.

The findings made researchers wonder if those susceptible to depression just needed a sufficient boost in electrical excitation in order to offset the excited neurons that seemed to be related to depression, so the team boosted runaway neuronal activity even further. As they had hoped, this eventually triggered a similar self-stabilizing response.

Even better, once electrical balance was restored, previously susceptible animals were no longer prone to becoming withdrawn, anxious, and listless following socially stressful experiences.

The discovery provides new insight into the cellular changes that likely occur in depressed individuals and suggests new directions for the development of antidepressants.

The study is published in Science.

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