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Nat Rev Neurosci. 2009 Jun;10(6):410-22. doi: 10.1038/nrn2648.

Stress signalling pathways that impair prefrontal cortex structure and function.

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  • 1Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.


The prefrontal cortex (PFC) - the most evolved brain region - subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.

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