Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Schizophr Bull. 2010 Mar;36(2):301-13. doi: 10.1093/schbul/sbp133. Epub 2009 Nov 10.
Schizophrenia is a condition that impairs higher brain functions, some of which are specific to humans. After identification of susceptibility genes for schizophrenia, many efforts have been made to generate genetics-based models for the disease. It is under debate whether behavioral deficits observed in rodents are sufficient to characterize these models. Alternatively, anatomical and neuropathological changes identified in brains of patients with schizophrenia may be utilized as translatable characteristics between humans and rodents, which are important for validation of the models. Here, we overview such anatomical and neuropathological changes in humans: enlarged ventricles, dendritic changes in the pyramidal neurons, and alteration of specific subtypes of interneurons. In this review, we will overview such morphological changes in brains from patients with schizophrenia. Then, we will describe that some of these alterations are already recapitulated even in classic nongenetic models for schizophrenia. Finally, in comparison with the changes in patients and nongenetic models, we will discuss the anatomical and neuropathological manifestation in genetic models for schizophrenia.
精神分裂症是一种损害大脑高级功能的疾病,其中一些功能是人类所特有的。在确定了精神分裂症的易感基因后,人们已经做出了许多努力,试图为这种疾病建立基于遗传学的模型。目前仍存在争议的是,在啮齿动物中观察到的行为缺陷是否足以描述这些模型。或者,在精神分裂症患者大脑中发现的解剖和神经病理学变化可以作为人类和啮齿动物之间的可转化特征,这对于模型的验证很重要。在这里,我们综述了人类中存在的这些解剖和神经病理学变化:脑室扩大、锥体神经元树突变化以及特定亚型中间神经元的改变。在这篇综述中,我们将综述精神分裂症患者大脑中的这些形态变化。然后,我们将描述其中一些改变即使在经典的非遗传精神分裂症模型中也已经被再现。最后,我们将比较患者和非遗传模型中的变化,讨论精神分裂症遗传模型中的解剖和神经病理学表现。