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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Corpus Callosum / cytology*
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Corticosterone / blood*
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Immunohistochemistry
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In Situ Hybridization
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Microscopy, Electron, Transmission
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Oligodendroglia / cytology*
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Oligodendroglia / metabolism*
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Oligodendroglia / ultrastructure
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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Restraint, Physical / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Stress, Physiological / physiology
Substances
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Cell Cycle Proteins
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Immediate-Early Proteins
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Intracellular Signaling Peptides and Proteins
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N-myc downstream-regulated gene 1 protein
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Pdk1 protein, mouse
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase
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Corticosterone