Differences of physical vs. psychological stress: evidences from glucocorticoid receptor expression, hippocampal subfields injury, and behavioral abnormalities.

The glucocorticoid receptor (GR) is the main effector of the activation of the hypothalamus-pituitary-adrenal (HPA) axis, which is caused by different types of stress that can be divided into two major categories: physical stress and psychological stress. Given the marked presence of GR in the hippocampus, GR-mediated hippocampal injury might be the core event under stress. The aim of this study was to investigate GR expression, hippocampal injury, and behaviors in rats to explore the differences between these types of stressors. Adult male rats were stressed using a classical model (electrical foot shock and a yoked psychologically stressful situation) to induce physical or psychological stress. The GR expression, injury of hippocampal subfields and behavioral abnormalities were dynamic, as demonstrated using immunofluorescence, 3D magnetic resonance imaging (MRI) and open field exploration (OFE), respectively. In addition, housing in a normal environment for 6 weeks was used to verify the recovery ability of rats. First, GR-mediated hippocampal atrophy and behavioral abnormalities were found in the second week under physical stress, but those changes did not appear until the fourth week under psychological stress. Second, the effects of stress were more pronounced after physical stressors than after psychological stressors in the fourth week, but this trend had reversed by the sixth week, especially in the DG (Dentate Gyrus) subfield. Except for the rats that had experienced 6 weeks of psychological stress, all rats showed significant recovery after 6 weeks of housing in a normal environment. The effects of physical stress appeared early but were relatively moderate, whereas the effects of psychological stress appeared late but were more severe. In addition, GR-mediated serious injury in the DG might be the cause of the DG volume loss and behaviors that could not be reversed.