common DNA methylation search of postmortem brain of individuals with schizophrenia and perinatal asphyxia-exposed rat model

精神分裂症个体和围产期窒息暴露大鼠模型死后脑部常见DNA甲基化搜索

• 批准号: 24659542
• 负责人: TAKEI noriyoshi
• 金额: $ 2.41万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659542/
• 关键词: 統合失調症; エピジェネティクス; 仮死モデル; DNMT

Epidemiological studies suggest that perinatal complications increase the risk of schizophrenia. Recent genetic studies have identified several putative susceptibility genes. 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 schizophrenia susceptibility genes. To test this, we used an animal model of perinatal asphyxia, and examined the expression of mRNA of five susceptibility genes 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. In addition, a significant increase in COMT mRNA expression was observed in the mPFC. 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.

流行病学研究表明，围产期并发症增加精神分裂症的风险。最近的遗传学研究已经确定了几个假定的易感基因。因此，可以推测，导致胎儿大脑缺氧的出生并发症可能与精神分裂症易感基因表达失调有关。为了验证这一点，我们使用了围产期窒息的动物模型，并检查了5个易感基因的mRNA表达的实时定量PCR在内侧前额叶皮层（mPFC）和海马在6和12周后出生。NRG 1 mRNA在mPFC中的表达显著降低，但在海马中的表达不明显。此外，在mPFC中观察到COMT mRNA表达的显著增加。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。

项目成果

Effect of Perinatal Asphyxia on Protein Expression in Rat Prefrontal Cortex during Postnatal Development

围产期窒息对产后发育过程中大鼠前额皮质蛋白表达的影响

• 发表时间: 2014
• 作者: Lam S;Wakuda T;Li Q;Wei R;Zhang X;Sham PC;Wang Y;Chua SE;Takei N and McAlonan GM
• 通讯作者: Takei N and McAlonan GM