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Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic–pituitary–adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both,  in vivo  and  in vitro : (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)–serum glucocorticoid regulated kinase (SGK1)– N -myc downstream-regulated gene 1 (NDRG1)–adhesion molecule (i.e.,  N -cadherin, α-catenin, and β-catenin) stabilization pathway  via  an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

Plasma Corticosterone Activates SGK1 and Induces Morphological Changes in Oligodendrocytes in Corpus Callosum