A form of DISC1 enriched in nucleus

Altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse

Naoya Sawamura, Takako Sawamura-Yamamoto, Yuji Ozeki, Christopher A. Ross, Akira Sawa

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Disrupted-In-Schizophrenia 1 (DISC1) was identified as the sole gene whose ORF is truncated and cosegregates with major mental illnesses in a Scottish family. DISC1 has also been suggested, by association and linkage studies, to be a susceptibility gene for schizophrenia (SZ) in independent populations. However, no analysis of DISC1 protein in human brains, especially those of patients with SZ, has yet been conducted. Here we performed a biochemical analysis of DISC1 protein in a well characterized set of autopsied brains, including brains of patients with SZ, bipolar disorder, and major depression (MD), as well as normal control brains. We identified an isoform of DISC1 by using MS and demonstrated that it is enriched in the nucleus of HeLa cells. In the orbitofrontal cortex, the subcellular distribution of this DISC1 isoform, assessed by the nuclear to cytoplasmic ratio in the immunoreactivity of the isoform, is significantly changed in brains from patients with SZ and MD. This altered distribution is also observed in those subjects with substance and alcohol abuse. The changes in MD brains are significantly influenced by substance/alcohol abuse as well as postmortem interval; however, the alteration in SZ brains is free from brain-associated confounding factors, although an interaction with substance/alcohol abuse cannot be completely ruled out. These results suggest that DISC1 may be implicated in psychiatric conditions in other populations than the unique Scottish family.

Original languageEnglish
Pages (from-to)1187-1192
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number4
DOIs
Publication statusPublished - 2005 Jan 25
Externally publishedYes

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Prefrontal Cortex
Psychotic Disorders
Alcoholism
Substance-Related Disorders
Schizophrenia
Brain
Protein Isoforms
Depression
Bipolar Disorder
HeLa Cells
Population
Open Reading Frames
Genes
Psychiatry

Keywords

  • Autopsied brains
  • Schizophrenia
  • Stanley foundation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A form of DISC1 enriched in nucleus : Altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse. / Sawamura, Naoya; Sawamura-Yamamoto, Takako; Ozeki, Yuji; Ross, Christopher A.; Sawa, Akira.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 4, 25.01.2005, p. 1187-1192.

Research output: Contribution to journalArticle

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