Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia.
Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a schizophrenia susceptibility gene. We measured mRNA expression levels of the three major isoforms of NRG-1 (ie type I, type II, and type III) in the postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and controls using real-time quantitative RT-PCR. Expression levels of three internal controls-GAPDH, cyclophilin, and beta-actin-were unchanged in schizophrenia, and there were no changes in the absolute levels of the NRG-1 isoforms. However, type I expression normalized by GAPDH levels was significantly increased in schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic medication dosage. Type II/type I and type II/type III ratios were significantly decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels of genotype at two SNPs previously associated with schizophrenia, suggesting that these alleles are not functionally responsible for abnormal NRG-1 expression patterns in patients. Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia.
Hashimoto
R
R
Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Straub
R E
RE
Weickert
C S
CS
Hyde
T M
TM
Kleinman
J E
JE
Weinberger
D R
DR
D001344:Autopsy; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics*; D020880:Neuregulins; D016133:Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C106766:NRG2 protein, human; C486357:NRG3 protein, human; D009414:Nerve Growth Factors; D020890:Neuregulin-1; D020880:Neuregulins; C491453:Nrg2 protein, mouse; D012333:RNA, Messenger