title: Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats.
abstract: Epidemiological studies suggest that perinatal complications, particularly hypoxia-related ones, increase the risk of schizophrenia. Recent genetic studies of the disorder have identified several putative susceptibility genes, some of which are known to be regulated by hypoxia. It can be postulated therefore that birth complications that cause hypoxia in the fetal brain may be associated with a dysregulation in the expression of some of the schizophrenia candidate genes. To test this, we used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Caesarean section birth, and examined the expression of mRNA of five of the putative susceptibility genes (NRG1, ErbB4, AKT1, COMT and BDNF) by real-time quantitative PCR in the medial prefrontal cortex (mPFC) and the hippocampus at 6 and 12 weeks after birth. The expression of NRG1 mRNA was significantly decreased in the mPFC, but not in the hippocampus, at 6 and 12 weeks after birth. In addition, a significant increase in COMT mRNA expression was observed in the mPFC at 12 weeks. The alteration in mRNA levels of NRG1 and COMT was not associated with a change in their protein levels. These results suggest that perinatal asphyxia may lead to disturbances in the PFC, which in turn may exert a long-lasting influence on the expression of specific genes, such as NRG1 and COMT. Our results also suggest that translational interruption may occur in this model of perinatal asphyxia.
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Wakuda
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Eiheiji-cho, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Mahesh Mundalil
authors.initials: MM
authors.lastname: Vasu
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Eiheiji-cho, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: k-suzuki@hama-med.ac.jp.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001237:Asphyxia / Q000378:metabolism / Q000473:pathology*; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020890:Neuregulin-1; D012333:RNA, Messenger; D002394:Catechol O-Methyltransferase
keywords: COMT; Neuregulin-1; Obstetric complications; Rat; Schizophrenia