title: Disturbance of oligodendrocyte function plays a key role in the pathogenesis of schizophrenia and major depressive disorder.
abstract: The major psychiatric disorders such as schizophrenia (SZ) and major depressive disorder (MDD) are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of SZ and MDD remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1) and DISC1 binding zinc finger (DBZ) might cause major psychiatric disorders such as SZ. Interestingly, both DISC and DBZ have been further detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 negatively regulates the differentiation of oligodendrocytes, whereas DBZ plays a positive regulatory role in oligodendrocyte differentiation. We have reported that repeated stressful events, one of the major risk factors of MDD, can induce sustained upregulation of plasma corticosterone levels and serum/glucocorticoid regulated kinase 1 (Sgk1) mRNA expression in oligodendrocytes. Repeated stressful events can also activate the SGK1 cascade and cause excess arborization of oligodendrocyte processes, which is thought to be related to depressive-like symptoms. In this review, we discuss the expression of DISC1, DBZ, and SGK1 in oligodendrocytes, their roles in the regulation of oligodendrocyte function, possible interactions of DISC1 and DBZ in relation to SZ, and the activation of the SGK1 signaling cascade in relation to MDD.
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, 337-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Shingo
authors.identifier: 0000-0001-8064-070X
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920-5111, Japan ; Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tsuyoshi
authors.identifier: 0000-0002-8168-8710
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, 337-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan ; Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Shoko
authors.identifier: 0000-0001-6524-3888
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, 337-2 Ohno-higashi, 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: D002454:Cell Differentiation / Q000235:genetics; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D008016:Life Change Events; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003345:Corticosterone; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C412476:DISC1 protein, human; C475725:ZNF365 protein, human