Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression

• Published in: Scientific reports Vol. 6; no. 1; p. 23084
• Main Authors: Miyata, Shingo, Taniguchi, Manabu, Koyama, Yoshihisa, Shimizu, Shoko, Tanaka, Takashi, Yasuno, Fumihiko, Yamamoto, Akihide, Iida, Hidehiro, Kudo, Takashi, Katayama, Taiichi, Tohyama, Masaya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2016; Nature Publishing Group
• Subjects: 101/28; 13/51; 13/89; 14/19; 38/109; 38/44; 38/77; 59/57; 631/378/1689/1414; 631/378/1831; 631/378/2596/1705; 692/699/476/1414; Adult; Animals; Anisotropy; Cell Adhesion Molecules, Neuronal - metabolism; Cells, Cultured; Corpus callosum; Corpus Callosum - diagnostic imaging; Corpus Callosum - metabolism; Corpus Callosum - pathology; Cyclic AMP; Depressive Disorder, Major - physiopathology; Depressive Disorder, Major - psychology; Female; Glucocorticoids; Glutamic acid receptors (metabotropic); Humanities and Social Sciences; Humans; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Kv1.1 Potassium Channel - metabolism; Magnetic Resonance Imaging; Male; Membrane potential; Mental depression; Mice, Inbred C57BL; Microscopy, Confocal; Middle Aged; multidisciplinary; Myelin; Nodes; Nodes of Ranvier; Oligodendroglia - metabolism; Oligodendroglia - pathology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Ranvier's Nodes - metabolism; Ranvier's Nodes - pathology; Rats, Wistar; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Science; Stress; Stress, Psychological - physiopathology; Substantia alba; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23084

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors ( mGluRs ). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs and that specific white matter abnormalities are closely associated with MDD onset.