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. 2014 May 15;9(5):e97689. doi: 10.1371/journal.pone.0097689

Figure 8. A model showing glucocorticoids plays different roles in the hippocampus and hypothalamus in modulating HPA axis activity under stressful state.

Figure 8

(A) An overview of the design to compare the roles of glucocorticoids in the hippocampus and hypothalamus in HPA axis hyperactivity and depressive-like behaviors. (B) A model describing the different roles of glucocorticoids in the hippocampus and hypothalamus in depression. The Acute stress stimulates glucocorticoids synthesis and releasing in adrenal cortex. Under acute stressful state, when glucocorticoids arriving in the hippocampus or hypothalamus, glucocorticoids exerts negative regulation of the synthesis of CRF in PVN neurons by GR. Under chronic stressful state, glucocorticoids in the hippocampus impair the negative feedback modulation of the synthesis of CRF in PVN neurons in the hypothalamus by disrupting hippocampal GR. However, glucocorticoids in the hypothalamus still exert negative regulation on the synthesis of CRF in PVN neurons. Glucocorticoids in the hippocampus disrupt GR function through MR-nNOS-NO pathway. (−) exerting negative regulation of HPA axis activity; (+) exerting positive regulation of HPA axis activity.