PUBLIC RELEASE DATE:

12-Nov-2014

Contact: Elizabeth Dowling newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine @mountsinainyc

The brain's ability to effectively deal with stress or to lack that ability and be more susceptible to depression, depends on a single protein type in each person's brain, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published November 12 in the journal Nature.

The Mount Sinai study findings challenge the current thinking about depression and the drugs currently used to treat the disorder.

"Our findings are distinct from serotonin and other neurotransmitters previously implicated in depression or resilience against it," says the study's lead investigator, Eric J. Nestler, MD, PhD, Nash Family Professor, Chair of the Department of Neuroscience and Director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. "These data provide a new pathway to find novel and potentially more effective antidepressants."

The protein involved in this new model of depression is beta-catenin (B-catenin), which is expressed throughout the brain and is known to have many biological roles. Using mouse models exposed to chronic social stress, Mount Sinai investigators discovered that it is the activity of the protein in the D2 neurons, a specific set of nerve cells (neurons) in the nucleus accumbens (NAc), the brain's reward and motivation center, which drives resiliency.

Specifically, the research team found that animals whose brains activated B-catenin were protected against stress, while those with inactive B-catenin developed signs of depression in their behavior. The study also showed suppression of this protein in brain tissue of depressed patients examined post mortem.

"Our human data are notable in that we show decreased activation of B-catenin in depressed humans, regardless of whether these individuals were on or off antidepressants at the time of death," says the study's co-lead investigator, Caroline Dias, an MD-PhD student at the Icahn School of Medicine at Mount Sinai. "This implies that the antidepressants were not adequately targeting this brain system."

In the study, researchers blocked B-catenin in the D2 brain cells in mice that had previously shown resilience to depression and found the animals became susceptible to stress. Conversely, activating B-catenin in stress mice bolstered their resilience to stress.

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Brain protein influences how the brain manages stress; suggests new model of depression