title: Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.
abstract: 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.
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.affiliation: Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Psychiatry, Osaka University Health Care Center, Toyonaka, Osaka 560-0043, Japan.|Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.|Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Suita, Osaka 565-0871, Japan.|Osaka Prefectural Hospital Organization, Osaka 558-8558, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D000328:Adult; D000818:Animals; D016880:Anisotropy; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D051662:Kv1.1 Potassium Channel / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008875:Middle Aged; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology*; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000503:physiopathology*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D017874:Immediate-Early Proteins; D051662:Kv1.1 Potassium Channel; D017346:Protein Serine-Threonine Kinases; D018094:Receptors, Metabotropic Glutamate; D000099184:Serum-Glucocorticoid Regulated Kinases; C491322:Cntnap1 protein, mouse