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Published on: July 11, 2025
Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats
Tomoyasu Wakuda1, Keiko Iwata2, Yasuhide Iwata1
1Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
Insights
Perinatal asphyxia, a birth complication, may alter schizophrenia risk by affecting gene expression in the brain. This study found lasting changes in NRG1 and COMT gene mRNA levels in rats after birth asphyxia.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Epidemiological studies link perinatal complications, especially hypoxia, to increased schizophrenia risk.
- Schizophrenia genetics research has identified susceptibility genes potentially regulated by hypoxia.
- Hypoxia during fetal development may dysregulate schizophrenia candidate gene expression.
Purpose of the Study:
- To investigate the long-term effects of perinatal asphyxia on schizophrenia candidate gene expression in an animal model.
- To examine mRNA levels of NRG1, ErbB4, AKT1, COMT, and BDNF in the medial prefrontal cortex (mPFC) and hippocampus.
Main Methods:
- Utilized an animal model of perinatal asphyxia (15 min intrauterine anoxia during C-section).
- Measured mRNA expression of five schizophrenia candidate genes (NRG1, ErbB4, AKT1, COMT, BDNF) using real-time quantitative PCR.
- Analyzed gene expression in the mPFC and hippocampus at 6 and 12 weeks post-birth.
Main Results:
- NRG1 mRNA expression was significantly decreased in the mPFC at 6 and 12 weeks.
- COMT mRNA expression was significantly increased in the mPFC at 12 weeks.
- Alterations in NRG1 and COMT mRNA levels were not accompanied by changes in protein levels, suggesting translational interruption.
Conclusions:
- Perinatal asphyxia can induce lasting disturbances in the medial prefrontal cortex.
- These disturbances may influence the long-term expression of specific genes like NRG1 and COMT, potentially impacting schizophrenia risk.
- The findings suggest that translational regulation may be disrupted in this perinatal asphyxia model.
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.
