Corticosteroid-induced gene expression is attenuated in the hippocampus of mice with model of post-traumatic stress disorder.

One of the distinctive features of post-traumatic stress disorder (PTSD) is an impairment of the hypothalamic-pituitary-adrenal (HPA) axis. Increased inhibition of cortisol synthesis after dexamethasone administration in patients indicates hyperactivation of the HPA feedback loop. This phenomenon may be explained by increased sensitivity of hypothalamic CRH-producing neurons to corticosteroids. Since corticosteroids signaling influences memory processing mechanisms, the issue of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors sensitivity is important for the pathogenesis of PTSD. Expression of both GR and MR target genes (Mt2, Fkbp5, and Jdp2) mRNA in hippocampal tissue of experimental mice was measured using RT-qPCR. The single prolonged stress (SPS) paradigm was used as an animal PTSD model. We found an attenuated expression of the GR negative regulator - co-chaperone Fkbp5 in animals after SPS exposure. When large doses of dexamethasone (5 mg/kg) or hydrocortisone (10 mg/kg) were administered, the expression of Mt2 and Fkbp5 increased in control mice, but not in the SPS group. There were no significant changes in Crh expression detected in all mice groups. This indicates lower transcriptional reactivity of GR, but not MR, in mice with the PTSD model, compared to the control group. Thus, our findings provide a new insight into the understanding of brain GR signaling in PTSD.