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Abnormal N-acetylglucosaminyltransferase expression in prefrontal cortex in schizophrenia.
- Source :
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Schizophrenia research [Schizophr Res] 2015 Aug; Vol. 166 (1-3), pp. 219-24. Date of Electronic Publication: 2015 Jun 20. - Publication Year :
- 2015
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Abstract
- Changes in the extent of the posttranslational modification glycosylation have been previously reported in several brain regions in schizophrenia. Quality control within the endoplasmic reticulum and Golgi, branching of glycans, intracellular trafficking and targeting, protein-protein interactions, and endocytosis are processes regulated by both N-linked and O-linked glycosylation. Previous studies in schizophrenia have found altered glycan biosynthesis and abnormal glycan levels in cerebrospinal fluid (CSF) and plasma, as well as altered expression in frontal cortex of glycosyltransferase transcripts encoding proteins associated with both N- and O-linked glycosylation. The N-acetylglucosaminyltransferases (GlcNAcTs) are glycosylating enzymes that play a key role in adding N-acetylglucosamine (GlcNAc) to substrates to facilitate their proper trafficking, intracellular targeting, and cellular function. Given previous results indicating abnormal glycosylation in schizophrenia, we hypothesized that these GlcNAcTs may be abnormally expressed in this illness. We measured protein expression of nine distinct GlcNAcTs by Western blot analysis in postmortem samples of dorsolateral prefrontal cortex (DLPFC) from twelve pairs of elderly patients with schizophrenia and comparison subjects. We found decreased protein expression of UDP-GlcNAc:BetaGal Beta-1,3 GlcNAcT 8 (B3GNT8) and mannosyl (alpha-1,3-)-glycoprotein beta-1,4 GlcNAcT (MGAT4A) expression in schizophrenia. These data provide further evidence that glycosylation is dysregulated in schizophrenia, and suggest a potential mechanism associated with alterations in protein function, trafficking, and intracellular targeting in this illness.<br /> (Published by Elsevier B.V.)
- Subjects :
- Aged
Animals
Antipsychotic Agents pharmacology
Antipsychotic Agents therapeutic use
Blotting, Western
Female
Gray Matter enzymology
Haloperidol analogs & derivatives
Haloperidol pharmacology
Haloperidol therapeutic use
Humans
Male
Prefrontal Cortex drug effects
Rats, Sprague-Dawley
Schizophrenia drug therapy
N-Acetylglucosaminyltransferases metabolism
Prefrontal Cortex enzymology
Schizophrenia enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2509
- Volume :
- 166
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Schizophrenia research
- Publication Type :
- Academic Journal
- Accession number :
- 26104473
- Full Text :
- https://doi.org/10.1016/j.schres.2015.06.002