Research discover mechanism for stress resilience

Scientists have discovered a mechanism that helps to explain resilience to stress, vulnerability to depression and how antidepressants work.

The new findings, in the reward circuit of mouse and human brains, have spurred a high tech dragnet for compounds that boost the action of a key gene regulator there, called deltaFosB.

A molecular main power switch -- called a transcription factor -- inside neurons, deltaFosB turns multiple genes on and off, triggering the production of proteins that perform a cell's activities.

"We found that triggering deltaFosB in the reward circuit's hub is both necessary and sufficient for resilience; it protects mice from developing a depression-like syndrome following chronic social stress," explained Eric Nestler, M.D., of the Mount Sinai School of Medicine, who led the research team, which was funded by the National Institute of Health's National Institute of Mental Health (NIMH).

"Antidepressants can reverse this social withdrawal syndrome by boosting deltaFosB. Moreover, deltaFosB is conspicuously depleted in brains of people who suffered from depression. Thus, induction of this protein is a positive adaptation that helps us cope with stress, so we're hoping to find ways to tweak it pharmacologically," added Nestler, who also directs the ongoing compound screening project.

Nestler and colleagues report the findings that inspired the hunt online May 16 2010 in the journal Nature Neuroscience.