Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats
Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats
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DOI：
10.1016/j.pnpbp.2014.08.002
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发表时间：
2015-01
影响因子：
5.6
通讯作者：
Tomoyasu Wakuda;Keiko Iwata;Y. Iwata;Ayyappan Anitha;Taro Takahashi;Kohei Yamada;M. Vasu;Hideo Matsuzaki;Katsuaki Suzuki;N. Mori
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文献类型：
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作者：
Tomoyasu Wakuda;Keiko Iwata;Y. Iwata;Ayyappan Anitha;Taro Takahashi;Kohei Yamada;M. Vasu;Hideo Matsuzaki;Katsuaki Suzuki;N. Mori
流行病学研究表明，围产期并发症，特别是与缺氧有关的并发症，增加了精神分裂症的风险。最近的遗传学研究的障碍已经确定了几个假定的易感基因，其中一些是已知的缺氧调节。因此，可以假设，导致胎儿大脑缺氧的出生并发症可能与某些精神分裂症候选基因表达的失调有关。为了验证这一点，我们使用了围产期窒息的动物模型，其中大鼠幼崽在剖腹产分娩期间暴露于15分钟的宫内缺氧，并通过实时定量PCR检测了出生后6周和12周内侧前额叶皮质（mPFC）和海马中5个假定易感基因（NRG 1，ErbB4，AKT1，COMT和BDNF）的mRNA表达。出生后6周和12周，mPFC中NRG 1 mRNA的表达显著降低，而海马中NRG 1 mRNA的表达无明显变化。此外，在12周时在mPFC中观察到COMT mRNA表达的显著增加。NRG 1和COMT mRNA水平的改变与其蛋白水平的变化无关。这些结果表明，围产期窒息可能会导致PFC的干扰，这反过来可能会对特定基因的表达产生长期的影响，如NRG 1和COMT。我们的研究结果还表明，翻译中断可能发生在这个模型的围产期窒息。
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.