Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress

• Published in: PLoS biology Vol. 13; no. 10; p. e1002282
• Main Authors: Licznerski, Pawel, Duric, Vanja, Banasr, Mounira, Alavian, Kambiz N., Ota, Kristie T., Kang, Hyo Jung, Jonas, Elizabeth A., Ursano, Robert, Krystal, John H., Duman, Ronald S.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2015; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Animals; Behavior, Animal; Brain research; Cohort Studies; Corticosteroids; Dendritic Spines - enzymology; Dendritic Spines - metabolism; Dendritic Spines - pathology; Depressive Disorder, Major - etiology; Development and progression; Dosage and administration; Drug therapy; Enzyme Repression; Female; Gene Transfer Techniques; Hippocampus - enzymology; Hippocampus - metabolism; Hippocampus - pathology; Humans; Immediate-Early Proteins - antagonists & inhibitors; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Kinases; Male; Middle Aged; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - enzymology; Neurons - metabolism; Neurons - pathology; Patient outcomes; Post traumatic stress disorder; Prefrontal Cortex - enzymology; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats, Sprague-Dawley; Rodents; Signal Transduction; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - pathology; Stress Disorders, Post-Traumatic - psychology; Synaptic Transmission; Tissue Banks; Maryland
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1002282

Exposure to extreme stress can trigger the development of major depressive disorder (MDD) as well as post-traumatic stress disorder (PTSD). The molecular mechanisms underlying the structural and functional alterations within corticolimbic brain regions, including the prefrontal cortex (PFC) and amygdala of individuals subjected to traumatic stress, remain unknown. In this study, we show that serum and glucocorticoid regulated kinase 1 (SGK1) expression is down-regulated in the postmortem PFC of PTSD subjects. Furthermore, we demonstrate that inhibition of SGK1 in the rat medial PFC results in helplessness- and anhedonic-like behaviors in rodent models. These behavioral changes are accompanied by abnormal dendritic spine morphology and synaptic dysfunction. Together, the results are consistent with the possibility that altered SGK1 signaling contributes to the behavioral and morphological phenotypes associated with traumatic stress pathophysiology.