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

• DOI: 10.1371/journal.pbio.1002282
• Publication Date: 2015-10-27T18:38:13Z
• Authors: Pawel Licznerski; Vanja Duric; Mounira Banasr; Kambiz N. Alavian; Kristie T. Ota; Hyo Jung Kang; Elizabeth A. Jonas; Robert Ursano; John H. Krystal; Ronald S. Duman
• Keywords: Life Sciences & Biomedicine - Other Topics; DISORDER; Adult; Male; Biochemistry & Molecular Biology; QH301-705.5; Dendritic Spines; LEARNED HELPLESSNESS; 150; 610; Prefrontal Cortex; Nerve Tissue Proteins; INDUCIBLE KINASE; Protein Serine-Threonine Kinases; CONDITIONED FEAR; Hippocampus; Immediate-Early Proteins; Cohort Studies; Rats, Sprague-Dawley; 03 medical and health sciences; WORKING-MEMORY; 0302 clinical medicine; Traumatic Stress Brain Study Group; THREONINE PROTEIN-KINASE; Animals; Humans; Biology (General); Biology; Neurons; Depressive Disorder, Major; Science & Technology; Behavior, Animal; MEDIAL PREFRONTAL CORTEX; HIPPOCAMPAL-NEURONS; Gene Transfer Techniques; PTSD; 11 Medical And Health Sciences; 06 Biological Sciences; Middle Aged; 3. Good health; EXTINCTION; Female; 07 Agricultural And Veterinary Sciences; Enzyme Repression; Life Sciences & Biomedicine; Developmental Biology; Research Article; Signal Transduction

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.