SGK1 knockdown in the medial prefrontal cortex reduces resistance to stress-induced memory impairment.

Down-regulation of serum and glucocorticoid-regulated kinase1 (SGK1) expression has been reported in the postmortem prefrontal cortex (PFC) of subjects with post-traumatic stress disorder. Furthermore, experimental treatments that reduce SGK1 function in the medial prefrontal cortex (mPFC) cause depressive-like behaviors and synaptic dysfunction. Therefore, we examined the effect of SGK1 down-regulation in the mPFC on resistance to stress-induced cognitive impairment. Rats with viral-mediated knockdown of SGK1 in the mPFC were subjected to either a brief 20-min restraint plus 20 intermittent tail shocks or a prolonged 60-min restraint plus 60 intermittent tail shocks, after which their performance in an object recognition task was assessed. Recognition memory remained intact in control rats following the brief stress, but was impaired in rats with SGK1 knockdown in the mPFC. Prolonged stress impaired recognition memory in both control rats and rats with SGK1 knockdown. Our findings indicate that altered mPFC SGK1 signaling is a potential mechanism for resistance to stress-induced cognitive impairment.