Perinatal Asphyxia in Rat Alters Expression of Novel Schizophrenia Risk Genes.
Perinatal Asphyxia in Rat Alters Expression of Novel Schizophrenia Risk Genes.
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DOI：
10.3389/fnmol.2017.00341
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发表时间：
2017
影响因子：
4.8
通讯作者：
Takei N
中科院分区：
文献类型：
--
作者：
Paparelli A;Iwata K;Wakuda T;Iyegbe C;Murray RM;Takei N
流行病学研究表明，产科并发症，特别是与分娩和分娩期间缺氧有关的并发症，是精神分裂症发生的危险因素。围产期窒息对出生后生活的影响已在啮齿动物模型的全面缺氧，这是伴随着剖宫产分娩。该窒息模型显示了成年期与精神分裂症相关的几种行为、药理学、神经化学和神经解剖学异常。此外，它表明，精神分裂症有很强的遗传成分，确实新的候选基因最近被确定的全基因组关联研究。在这里，我们研究了新的精神分裂症风险基因，CNNM 2，CSMD 1和MMP 16在接受剖腹产手术的大鼠大脑中的变化，有或没有全面缺氧。研究的大脑区域是前额皮质、纹状体和海马体，这些都与精神分裂症有关。在三个时间段测量风险基因表达：新生儿，青春期和成年期。我们还进行了体外分析，以确定这些基因在人神经元和神经胶质细胞系分化过程中参与CNS成熟。Cnnm 2在窒息模型大鼠脑内表达改变。然而，Csmd 1和Mmp 16的表达改变暴露于剖宫产术。这些发现表明，这些风险基因的表达改变，通过窒息和剖宫产可能与精神分裂症的病理生物学，虽然通过不同的途径。
Epidemiological studies suggest that obstetric complications, particularly those related to hypoxia during labor and delivery, are a risk factor for development of schizophrenia. The impact of perinatal asphyxia on postnatal life has been studied in a rodent model of global hypoxia, which is accompanied by cesarean section birth. This asphyxia model shows several behavioral, pharmacological, neurochemical, and neuroanatomical abnormalities in adulthood that have relevance to schizophrenia. Further, it is suggested that schizophrenia has a strong genetic component, and indeed novel candidate genes were recently identified by a genome-wide association study. Here, we examined alteration in the novel schizophrenia risk genes, CNNM2, CSMD1, and MMP16 in the brains of rats undergoing cesarean section with or without global hypoxia. The brain regions studied were the prefrontal cortex, striatum, and hippocampus, which are all relevant to schizophrenia. Risk gene expression was measured at three time periods: neonatal, adolescence, and adulthood. We also performed an in vitro analysis to determine involvement of these genes in CNS maturation during differentiation of human neuronal and glial cell lines. Cnnm2 expression was altered in the brains of asphyxia model rats. However, Csmd1 and Mmp16 showed altered expression by exposure to cesarean section only. These findings suggest that altered expression of these risk genes via asphyxia and cesarean section may be associated, albeit through distinct pathways, with the pathobiology of schizophrenia.
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影响因子：
5.3
作者：
Brake, WG;Sullivan, RM;Gratton, A
通讯作者：
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4.5
作者：
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通讯作者：
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作者：
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通讯作者：
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