Tomoda T, Sumitomo A, Jaaro-Peled H, Sawa A
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Neuroscience. 2016 May 3;321:99-107. doi: 10.1016/j.neuroscience.2015.12.061. Epub 2016 Jan 6.
We have seen an era of explosive progress in translating neurobiology into etiological understanding of mental disorders for the past 10-15 years. The discovery of Disrupted-in-schizophrenia 1 (DISC1) gene was one of the major driving forces that have contributed to the progress. The finding that DISC1 plays crucial roles in neurodevelopment and synapse regulation clearly underscored the utility and validity of DISC1-related biology in advancing our understanding of pathophysiological processes underlying psychiatric conditions. Despite recent genetic studies that failed to identify DISC1 as a risk gene for sporadic cases of schizophrenia, DISC1 mutant mice, coupled with various environmental stressors, have proven successful in satisfying face validity as models of a wide range of human psychiatric conditions. Investigating mental disorders using these models is expected to further contribute to the circuit-level understanding of the pathological mechanisms, as well as to the development of novel therapeutic strategies in the future.
在过去的10到15年里,我们见证了一个将神经生物学转化为对精神障碍病因学理解的爆炸式发展的时代。精神分裂症相关1基因(DISC1)的发现是推动这一进展的主要驱动力之一。DISC1在神经发育和突触调节中起关键作用这一发现,清楚地强调了DISC1相关生物学在推进我们对精神疾病潜在病理生理过程理解方面的实用性和有效性。尽管最近的基因研究未能将DISC1确定为散发性精神分裂症病例的风险基因,但DISC1突变小鼠与各种环境应激源相结合,已被证明成功地满足了作为多种人类精神疾病模型的表面效度。利用这些模型研究精神障碍有望在未来进一步促进对病理机制的回路水平理解,以及新治疗策略的开发。