Oxygen restriction of neonate rats elevates neuregulin-1alpha isoform levels: possible relationship to schizophrenia.
Neuregulin-1 (NRG-1), a replicated gene in schizophrenia-association studies, exhibits six mRNA-types and two types of the EGF-like domain, alpha and beta. The beta-isoform was extensively studied, less is known about the extent and specific localization of adult brain NRG-1alpha. NRG-1alpha protein levels were reported reduced in postmortem prefrontal-cortex of schizophrenia patients. NRG-1 type I mRNA levels were found higher in postmortem brain in schizophrenia. In an attempt to decipher between a genetic or environmental involvement in the differences in NRG-1 levels in postmortem brain in schizophrenia, and since obstetric complications were suggested non-genetic risk-factors of schizophrenia, we studied the effect of perinatal hypoxia in rats on brain NRG-1alpha protein levels. Seven-day-old rats were exposed to hypoxia versus air. Frontal-cortex levels of NRG-1alpha isoform were quantified at adulthood by Western blotting. Frontal-cortex NRG-1alpha was 32% elevated in hypoxia-exposed rats. The data support the role of non-genetic factors, e.g. oxygen restriction, in the expression of genes associated with schizophrenia.
Nadri
Carmit
C
Stanley Research Center, Faculty of Health Science, Ben-Gurion University of the Negev, and Mental Health Center, Beersheva, Israel.
Belmaker
R H
RH
Agam
Galila
G
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D015984:Causality; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020890:Neuregulin-1; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D020033:Protein Isoforms