title: Sgk1 regulates desmoglein 1 expression levels in oligodendrocytes in the mouse corpus callosum after chronic stress exposure.
abstract: Major depression, one of the most prevalent mental illnesses, is thought to be a multifactorial disease related to both genetic and environmental factors. However, the genes responsible for and the pathogenesis of major depression at the molecular level remain unclear. Recently, we reported that stressed mice with elevated plasma corticosterone levels show upregulation and activation of serum glucocorticoid-regulated kinase (Sgk1) in oligodendrocytes. Active Sgk1 causes phosphorylation of N-myc downstream-regulated gene 1 (Ndrg1), and phospho-Ndrg1 increases the expression of N-cadherin, α-catenin, and β-catenin in oligodendrocytes. This activation of the Sgk1 cascade results in morphological changes in the oligodendrocytes of nerve fiber bundles, such as those present in the corpus callosum. However, little is known about the molecular functions of the traditional and/or desmosomal cadherin superfamily in oligodendrocytes. Therefore, in this study, we aimed to elucidate the functions of the desmosomal cadherin superfamily in oligodendrocytes. Desmoglein (Dsg) 1, Dsg2, and desmocollin 1 (Dsc1) were found to be expressed in the corpus callosum of mouse brain, and the expression of a subtype of Dsg1, Dsg1c, was upregulated in oligodendrocytes after chronic stress exposure. Furthermore, Dsg1 proteins were localized around the plasma membrane regions of oligodendrocytes. A study in primary oligodendrocyte cultures also revealed that chronic upregulation of Sgk1 by dexamethasone administration is involved in upregulation of Dsg1c mRNA. These results may indicate that chronic stress induced Sgk1 activation in oligodendrocytes, which increases Dsg1 expression near the plasma membrane. Thus, Dsg1 upregulation may be implicated in the molecular mechanisms underlying the morphological changes in oligodendrocytes in response to chronic stress exposure.
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan. Electronic address: smiyata@med.kindai.ac.jp.
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: Keiko
authors.initials: K
authors.lastname: Yoshikawa
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: Toshiko
authors.initials: T
authors.lastname: Ishikawa
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: 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; Osaka Prefectural Hospital Organization, Osaka, 558-8558, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism* / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism*; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D003345:Corticosterone; D051183:Desmoglein 1; D051301:Desmoglein 2; D003907:Dexamethasone; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D051178:alpha Catenin; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C495267:CTNNB1 protein, mouse; C489083:Cdh2 protein, mouse; C478363:Dsg1c protein, mouse; C495315:Dsg2 protein, mouse
keywords: Chronic stress; Desmosome; Major depression; Oligodendrocytes; Sgk1