Neuronal migration abnormalities and its possible implications for schizophrenia.
Neuronal migration abnormalities and its possible implications for schizophrenia.
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DOI：
10.3389/fnins.2015.00074
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发表时间：
2015
影响因子：
4.3
通讯作者：
Tanigaki K
中科院分区：
文献类型：
--
作者：
Muraki K;Tanigaki K
精神分裂症是一种复杂的精神障碍，表现出行为缺陷，如感觉门控减少，社会互动减少和工作记忆缺陷。神经发育模型是精神分裂症病因学的一个被广泛接受的假说。在临床症状出现之前很久就出现的大脑微妙发育异常被认为是导致疾病出现的原因。精神分裂症有很强的遗传成分，但其潜在的分子发病机制仍然知之甚少。遗传连锁和关联研究已经确定了几个参与神经元迁移的基因作为精神分裂症的候选易感基因，尽管它们的效应量很小。拷贝数变异研究的最新进展也确定了高得多的风险位点，如22q11。基于这些遗传学发现，我们现在能够利用遗传学定义的动物模型。在这里，我们总结了遗传定义的动物模型的神经发育和行为分析的结果。此外，动物模型实验表明，胚胎和围产期神经发育损伤的神经发生和神经元迁移导致神经元功能和行为缺陷的影响成年动物，这是类似的精神分裂症患者。然而，这些发现并不能确定因果关系。遗传定义的动物模型是探索神经元迁移异常与精神分裂症相关行为异常之间关系的重要方法。
Schizophrenia is a complex mental disorder that displays behavioral deficits such as decreased sensory gating, reduced social interaction and working memory deficits. The neurodevelopmental model is one of the widely accepted hypotheses of the etiology of schizophrenia. Subtle developmental abnormalities of the brain which stated long before the onset of clinical symptoms are thought to lead to the emergence of illness. Schizophrenia has strong genetic components but its underlying molecular pathogenesis is still poorly understood. Genetic linkage and association studies have identified several genes involved in neuronal migrations as candidate susceptibility genes for schizophrenia, although their effect size is small. Recent progress in copy number variation studies also has identified much higher risk loci such as 22q11. Based on these genetic findings, we are now able to utilize genetically-defined animal models. Here we summarize the results of neurodevelopmental and behavioral analysis of genetically-defined animal models. Furthermore, animal model experiments have demonstrated that embryonic and perinatal neurodevelopmental insults in neurogenesis and neuronal migrations cause neuronal functional and behavioral deficits in affected adult animals, which are similar to those of schizophrenic patients. However, these findings do not establish causative relationship. Genetically-defined animal models are a critical approach to explore the relationship between neuronal migration abnormalities and behavioral abnormalities relevant to schizophrenia.
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DOI：
10.1523/jneurosci.1815-08.2008
发表时间：
2008-07-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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影响因子：
11
作者：
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通讯作者：
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DOI：
10.1073/pnas.1010669107
发表时间：
2010-12-14
影响因子：
11.1
作者：
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DOI：
10.1073/pnas.0609440103
发表时间：
2006-12-26
影响因子：
11.1
作者：
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通讯作者：
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