Ahmad Ruhel, Sportelli Vincenza, Ziller Michael, Spengler Dietmar, Hoffmann Anke
Max Planck Institute of Psychiatry, Translational Psychiatry, 80804 Munich, Germany.
Cells. 2018 Sep 17;7(9):140. doi: 10.3390/cells7090140.
Schizophrenia (SCZ) is a devastating mental disorder that is characterized by distortions in thinking, perception, emotion, language, sense of self, and behavior. Epidemiological evidence suggests that subtle perturbations in early neurodevelopment increase later susceptibility for disease, which typically manifests in adolescence to early adulthood. Early perturbations are thought to be significantly mediated through incompletely understood genetic risk factors. The advent of induced pluripotent stem cell (iPSC) technology allows for the in vitro analysis of disease-relevant neuronal cell types from the early stages of human brain development. Since iPSCs capture each donor's genotype, comparison between neuronal cells derived from healthy and diseased individuals can provide important insights into the molecular and cellular basis of SCZ. In this review, we discuss results from an increasing number of iPSC-based SCZ/control studies that highlight alterations in neuronal differentiation, maturation, and neurotransmission in addition to perturbed mitochondrial function and micro-RNA expression. In light of this remarkable progress, we consider also ongoing challenges from the field of iPSC-based disease modeling that call for further improvements on the generation and design of patient-specific iPSC studies to ultimately progress from basic studies on SCZ to tailored treatments.
精神分裂症（SCZ）是一种具有破坏性的精神障碍，其特征在于思维、感知、情感、语言、自我意识和行为的扭曲。流行病学证据表明，早期神经发育中的细微扰动会增加日后患该病的易感性，该病通常在青春期至成年早期表现出来。早期扰动被认为主要是通过尚未完全了解的遗传风险因素介导的。诱导多能干细胞（iPSC）技术的出现使得从人类大脑发育早期阶段对与疾病相关的神经元细胞类型进行体外分析成为可能。由于iPSC捕获了每个供体的基因型，因此来自健康个体和患病个体的神经元细胞之间的比较可以为精神分裂症的分子和细胞基础提供重要见解。在这篇综述中，我们讨论了越来越多基于iPSC的精神分裂症/对照研究的结果，这些研究除了突出线粒体功能和微小RNA表达受到干扰外，还强调了神经元分化、成熟和神经传递的改变。鉴于这一显著进展，我们还考虑了基于iPSC的疾病建模领域当前面临的挑战，这些挑战要求在患者特异性iPSC研究的生成和设计方面进一步改进，以最终从精神分裂症的基础研究迈向量身定制的治疗方法。
