Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2015-01, Vol.56, p.149-154
• Main Authors: Wakuda, Tomoyasu, Iwata, Keiko, Iwata, Yasuhide, Anitha, Ayyappan, Takahashi, Taro, Yamada, Kohei, Vasu, Mahesh Mundalil, Matsuzaki, Hideo, Suzuki, Katsuaki, Mori, Norio
• Format: Article
• Language: English
• Subjects: Age Factors; Analysis of Variance; Animals; Asphyxia - metabolism; Asphyxia - pathology; Catechol O-Methyltransferase - genetics; Catechol O-Methyltransferase - metabolism; COMT; Female; Gene Expression Regulation - physiology; Male; Neuregulin-1; Neuregulin-1 - genetics; Neuregulin-1 - metabolism; Obstetric complications; Prefrontal Cortex - metabolism; Pregnancy; Rat; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Schizophrenia
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2014.08.002

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 15min 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 12weeks after birth. The expression of NRG1 mRNA was significantly decreased in the mPFC, but not in the hippocampus, at 6 and 12weeks after birth. In addition, a significant increase in COMT mRNA expression was observed in the mPFC at 12weeks. 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. •NRG1 and COMT are putative susceptibility genes for SZ and regulated by hypoxia.•We examine the expression of NRG1 and COMT mRNA in perinatal asphyxia model rats.•The expression of NRG1 mRNA was decreased in the mPFC at 6 and 12 weeks of age.•The expression of COMT mRNA was increased in the mPFC at 12 weeks of age.•The hippocampus showed no change in the mRNA levels.