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01-06-2015 | Review Article

Molecular basis of major psychiatric diseases such as schizophrenia and depression

Authors: Masaya Tohyama, Shingo Miyata, Tsuyoshi Hattori, Shoko Shimizu, Shinsuke Matsuzaki

Published in: Anatomical Science International | Issue 3/2015

Abstract

Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported. DISC1 is involved in neural development directly via adhesion molecules or via its binding partners of DISC1 such as elongation protein ζ-1 (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates neural development via stathmin 1 or via regulation of the DISC1-DBZ binding. Dysbindin is also involved in neural development by regulating centrosomal microtubule network formation. All such molecules examined to date are involved in neural development. Thus, these findings provide new molecular insights into the mechanisms of neural development and neuropsychiatric disorders. On the other hand, in addition to neurons, both DISC and DBZ have been detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 inhibits the differentiation of oligodendrocyte precursor cells into oligodendrocytes, while DBZ has a positive regulatory role in oligodendrocyte differentiation. Evidence suggesting that disturbance of oligodendrocyte development causes major depression is also described.

Anitha A, Nakamura K, Yamada K et al (2008) Gene expression analyses reveal enhanced expression of pericentrin2 (PCNT2) in bipolar disorder. Biol Psychiatry 63:678–685CrossRefPubMed

Anitha A, Nakamura K, Yamada K et al (2009) Association studies and gene expression analysis of the DISC1-interacting molecules, Precentin2 (PCNT2) and DISC1-binding zinc finger protein (DBZ), with schizophrenia and with bipolar disorder. Am J Med Genet B 150:967–976CrossRef

Aston C, Jiang I, Sokolove BP (2005) Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry 10:309–322CrossRefPubMed

Brandon NJ, Handford EJ, Schurov I et al (2004) Disrupted-In-Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol Cell Neurosci 25:42–55CrossRefPubMed

Cannon TD, Hennah W, van Erp TG et al (2005) Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Arch Gen Psychiatry 8:685–694

Cardinaux JR, Magistretti PJ, Martin JL (1997) Brain-derived neurotrophic factor stimulates phosphorylation of stathmin in cortical neurons. Mol Brain Res 51: 220–228CrossRefPubMed

Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK (2008) The DISC1 locus in psychiatric illness. Mol Psychiatry 13:36–64CrossRefPubMed

Feng YQ, Zhou ZY, He X et al (2008) Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia. Schizophr Res 106:218–228CrossRefPubMed

Hamidi M, Drevets WC, Price JI (2004) Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 55:563–569CrossRefPubMed

Hashimoto H, Shintani N, Tanaka K et al (2001) Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci USA 98:1335–13360CrossRef

Hashimoto R, Hashimoto H, Shintani N et al (2007) Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia. Mol Psychiatry 12:1026–1032CrossRefPubMed

Hattori T, Baba K, Matsuzaki S et al (2007) A novel DISC1-interacting partner DISC1 binding zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Mol Psychiatry 12:398–407CrossRefPubMed

Hattori S, Murotani T, Matsuzaki S et al (2008) Behavioral abnormalities and dopamine reductions in sdy mice with a deletion inDtnbp1, a susceptibility gene for schizophrenia. Biochem Biophys Res Commun 373:298–302CrossRefPubMed

Hattori T, Shimizu N, Koyama Y et al (2010) DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth. Mol Psychiatry 15:1–12CrossRef

Hattori T, Shimizu S, Koyama Y et al (2014) DISC1 (Disrupted-in-schizophrenia-1) regulate differentiation of oligodendrocytes. PLoS One 9:e88508CrossRef

Hodgkinson CA, Goldman D, Jaeger J et al (2004) (2004) Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 75(5):862–872CrossRefPubMedCentralPubMed

Honda A, Miyoshi K, Baba K et al (2004) Expression of fasciculation and elongation protein zeta-1 (FEZ1) in the developing brain. Brain Res Mol Brain Res 122:89–92CrossRefPubMed

Jaaro-Peled H, Hayashi-Takagi A, Seshadri S, Kamiya A, Brandon NJ, Sawa A (2009) Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1. Trends Neurosci 32:485–495CrossRefPubMedCentralPubMed

Katayama T, Hattori T, Yamada K, Matsuzaki S (2009) Tohyama M (2009) The role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin 1 systems in schizophrenia and bipolar disorder: novel treatment mechanisms? Pharmacogenomics 10(12):1967–1978CrossRefPubMed

Koyama Y, Hattori T, Shimizu S et al (2013) DBZ (DISC1-binding zinc finger protein)-deficient mice display abnormalities in basket cells in the somatosensory cortices. J Chem Neuroanat 53:1–10CrossRefPubMed

Kubota K, Kumamoto N, Matsuzaki S et al (2009) Dysbindin engages in c-Jun N terminal kinase activity and cytoskeletal organization. Biochem Biophys Res Commun 379:191–195CrossRefPubMed

Kumamoto N, Matsuzaki S, Inoue K et al (2006) Heperactivation of midbrain dopaminergic system in schizophrenia could be attributed to the down-regulation of dysbindin. Biochem Biophys Res Commun 345:904–909CrossRefPubMed

Lacerda AL, Brambilla P, Sassi RB et al (2005) Anatomical MRI study of corpus callosum in unipolar depression. J Psychiatr Res 39:47–354CrossRef

Miyata S, Koyama Y, Tatemoto et al (2011) Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum. PLoS One 6:e19859CrossRefPubMedCentralPubMed

Miyata S, Hattori T, Shimizu S, Ito A, Tohyama M (2015) Disturbance of oligodendrocyte function plays a key role in the pathogenesis of major psychiatric diseases. BioMed Res Int Article ID 492367 (in press)

Miyoshi K, Honda A, Baba K et al (2003) Disrupted-in-schizophrenia 2, a candidate gene for schizophrenia, participates in neurite outgrowth. Mol Psychiatry 8:685–694CrossRefPubMed

Miyoshi K, Asanuma M, Miyazaki I et al (2004) DISC1 localizes to the centrosome by binding to kendrin. Bichem Biophys Res Commun 317:1195–1199CrossRef

Nicot A, Otto T, Braber P, Dicicco-Bloom EM (2004) Altered social behavior in pituitary adenylate cyclase-activating polypeptide type1 receptor-deficient mice. J Neurosci 24:8786–8795CrossRefPubMed

Numakawa T, Yagasaki Y, Ihimoto T et al (2004) Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 13:2699–2708CrossRefPubMed

Okamoto M, Hattori T, Matsuzaki S et al. (2015) DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation. J Neurosci (in press)

Okuda H, Kuwahara R, Matsuzaki S et al (2010) Transcriptional level of myristoylated alanine-rich protein kinase C substrate via the interaction with NF-YB in mice brain. PLoS One 5:e8773CrossRefPubMedCentralPubMed

Ozeki Y, Tomoda T, Kleiderlein J et al (2003) Disrupted-in-Schizophrenia 1 (DISC1): mutant truncation presents binding to NudelE-like (NUDEL) and inhibits neurite outgrowth. Proc Natl Acad Sci USA 100:289–294CrossRefPubMedCentralPubMed

Shimizu S, Matsuzaki S, Hattori T et al (2008) DISC1-kendrin interaction is involved in centrosomal microtubule network formation. Biochem Biophys Res Commun 377:1051–1056CrossRefPubMed

Shimizu S, Koyama Y, Hattori T et al (2014) DBZ, a CNS-specific DISC1 binding protein, positively regulate oligodendrocyte differentiation. Glia 62:709–724CrossRefPubMed

Shinoda T, Taya S, Tsuboi D et al (2007) DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. J Neurosci 27:4–14CrossRefPubMed

Straub Y, Jiang CJ, MacLean Y et al (2002) Genetic variation in the 6p22.3 gene DNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 71:337–348CrossRefPubMedCentralPubMed

Taya S, Shinoda T, Tsuboi D et al (2007) DISC1 regulated the transport of the NUDEL/LIS1? 14-3-3epsilon complex through linesin 1. J Neurosci 27:15–26CrossRefPubMed

Wan S, Sun CE, Walczak CA et al (1995) Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22. Nat Genet 10:41–46CrossRef

Yamada K, Nakamura K, Minabe Y et al (2004) Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts. Biol Psychiatry 56:683–690CrossRefPubMed

Yamada K, Matsuzaki S, Hattori T et al (2010) Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations. PLoS ONE 5:e8596CrossRefPubMedCentralPubMed

Title: Molecular basis of major psychiatric diseases such as schizophrenia and depression
Authors: Masaya Tohyama
Shingo Miyata
Tsuyoshi Hattori
Shoko Shimizu
Shinsuke Matsuzaki
Publication date: 01-06-2015
Publisher: Springer Japan
Published in: Anatomical Science International / Issue 3/2015
Print ISSN: 1447-6959
Electronic ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-014-0269-3

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Molecular basis of major psychiatric diseases such as schizophrenia and depression

Abstract

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Abstract

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