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Feb 14, 2013
 |  BC Innovations  |  Targets & Mechanisms

Stressing out over depression and anxiety

Two teams have shown that enhanced glucocorticoid signaling in the brain triggers aberrant behavior in mouse models of depression and anxiety.1,2 The groups are now using the mice to study the mechanisms underlying the effect and determine whether blocking glucocorticoid signaling can treat neuropsychiatric diseases.

All mammals respond to stress by releasing glucocorticoids from the adrenal glands. Although that stress mechanism is beneficial when it facilitates the fight or flight response, chronic activation of the glucocorticoid response can trigger multiple neuropsychiatric disorders in humans, including pathological anxiety, depression and addiction.

The challenge has been identifying the molecular mechanisms underlying chronic activation of the glucocorticoid-mediated stress response and determining whether blocking that mechanism could help treat those disorders. Moreover, because the glucocorticoid receptor (GCCR) is a transcription factor expressed in many different cell types, safely targeting it in neuropsychiatric disorders will require selectively hitting specific neurons in the brain.

To tackle those issues, two groups generated genetically altered mice and subjected them to environmental conditions predicted to trigger stress-mediated anxiety and depression in humans.

The French group, led by François Tronche and Jacques Barik, built on their prior work that showed selectively knocking out Gccr in postsynaptic, dopamine-sensing neurons decreased cocaine addiction in mice compared with what was seen in control mice.3 Dopamine signaling in...

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