title: Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.
abstract: 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.
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. smiyata@anat2.med.osaka-u.ac.jp
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.forename: Kana
authors.initials: K
authors.lastname: Takemoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Toshiko
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Inoue
authors.forename: Miwa
authors.initials: M
authors.lastname: Aoki
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003337:Corpus Callosum / Q000166:cytology*; D003345:Corticosterone / Q000097:blood*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012149:Restraint, Physical / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D003345:Corticosterone; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C000631433:Pdk1 protein, mouse