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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-7-15
pubmed:abstractText
Cortical GABA deficits that are consistently reported in schizophrenia may reflect an etiology of failed normal postnatal neurotransmitter maturation. Previous studies have found prefrontal cortical GABA(A) receptor alpha subunit alterations in schizophrenia, yet their relationship to normal developmental expression profiles in the human cortex has not been determined. The aim of this study was to quantify GABA(A) receptor alpha-subunit mRNA expression patterns in human dorsolateral prefrontal cortex (DLPFC) during normal postnatal development and in schizophrenia cases compared to controls. Transcript levels of GABA(A) receptor alpha subunits were measured using microarray and qPCR analysis of 60 normal individuals aged 6weeks to 49years and in 37 patients with schizophrenia/schizoaffective disorder and 37 matched controls. We detected robust opposing changes in cortical GABA(A) receptor alpha1 and alpha5 subunits during the first few years of postnatal development, with a 60% decrease in alpha5 mRNA expression and a doubling of alpha1 mRNA expression with increasing age. In our Australian schizophrenia cohort we detected decreased GAD67 mRNA expression (p=0.0012) and decreased alpha5 mRNA expression (p=0.038) in the DLPFC with no significant change of other alpha subunits. Our findings confirm that GABA deficits (reduced GAD67) are a consistent feature of schizophrenia postmortem brain studies. Our study does not confirm alterations in cortical alpha1 or alpha2 mRNA levels in the schizophrenic DLPFC, as seen in previous studies, but instead we report a novel down-regulation of alpha5 subunit mRNA suggesting that post-synaptic alterations of inhibitory receptors are an important feature of schizophrenia but may vary between cohorts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1879-1379
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
673-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20100621-Adolescent, pubmed-meshheading:20100621-Adult, pubmed-meshheading:20100621-Age Distribution, pubmed-meshheading:20100621-Analysis of Variance, pubmed-meshheading:20100621-Australia, pubmed-meshheading:20100621-Cadaver, pubmed-meshheading:20100621-Child, pubmed-meshheading:20100621-Child, Preschool, pubmed-meshheading:20100621-Cohort Studies, pubmed-meshheading:20100621-Gene Expression, pubmed-meshheading:20100621-Human Development, pubmed-meshheading:20100621-Humans, pubmed-meshheading:20100621-Infant, pubmed-meshheading:20100621-Middle Aged, pubmed-meshheading:20100621-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20100621-Polymerase Chain Reaction, pubmed-meshheading:20100621-Prefrontal Cortex, pubmed-meshheading:20100621-Receptors, GABA-A, pubmed-meshheading:20100621-Schizophrenia, pubmed-meshheading:20100621-Young Adult
pubmed:year
2010
pubmed:articleTitle
Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia.
pubmed:affiliation
Schizophrenia Research Institute, Sydney 2021, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't