Neuronal migration abnormalities and its possible implications for schizophrenia

• Main Authors: Kenji eTanigaki, Kazue eMuraki
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-03-01
• Series: Frontiers in Neuroscience
• Subjects: 22q11 Deletion Syndrome; Schizophrenia; CXCR4; DISC1; mouse models; DGCR8
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00074/full

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.