title: Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia.
abstract: Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.
authors: Department of Psychiatry, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany. hans-gert.bernstein@med.ovgu.de.
authors: Hans-Gert
authors: HG
authors: Bernstein
authors: Department of Psychiatry, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Esther
authors: E
authors: Jauch
authors: Department of Psychiatry, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Henrik
authors: H
authors: Dobrowolny
authors: Institute for Neuropathology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Christian
authors: C
authors: Mawrin
authors: Department of Psychiatry, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Johann
authors: J
authors: Steiner
authors: Department of Psychiatry, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Bernhard
authors: B
authors: Bogerts
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D010296:Parietal Lobe / Q000473:pathology*; D012563:Schizophrenia, Paranoid / Q000473:pathology*; D018709:Statistics, Nonparametric; D066127:White Matter / Q000473:pathology*
chemical_list: C412476:DISC1 protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases
keywords: Disrupted-in-schizophrenia 1 (DISC1); Immunohistochemistry; Paranoid schizophrenia; Schizophrenia; White matter oligodendroglia