Modeling synaptogenesis in schizophrenia and autism using human iPSC derived neurons.
Modeling synaptogenesis in schizophrenia and autism using human iPSC derived neurons.
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DOI：
10.1016/j.mcn.2015.12.002
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Ming GL
中科院分区：
文献类型：
--
作者：
Habela CW;Song H;Ming GL
精神分裂症（SCZ）和自闭症谱系障碍（ASD）是神经发育方面具有遗传和表型复杂性的疾病。人类遗传学研究以及在细胞水平检测结构变化的研究都聚焦于谷氨酸能突触的形成、功能和维持，将其作为这两种疾病共同的病理生理基础。突触作为大脑的基本功能单位，在整个生命过程中会不断因经历而发生改变，因此它们是靶向治疗极具吸引力的候选对象。直到最近，我们还缺乏一个系统来评估导致突触异常的动态变化。随着从患者身上产生诱导多能干细胞（iPSCs）技术的发展，我们现在能够在赋予疾病易感性的基因变化背景下研究个体患者细胞中的神经元和突触发育。在这篇综述中，我们讨论了近期专注于从精神分裂症和自闭症谱系障碍患者的诱导多能干细胞分化出的神经细胞的研究。这些研究支持了谷氨酸能突触的形成和功能在这两种疾病中的核心作用，并表明诱导多能干细胞衍生的神经元为进一步评估导致突触失调的过程以及未来治疗方法的设计和筛选提供了一个潜在的系统。
Schizophrenia (SCZ) and autism spectrum disorder (ASD) are genetically and phenotypically complex disorders of neural development. Human genetic studies, as well as studies examining structural changes at the cellular level, have converged on glutamatergic synapse formation, function, and maintenance as common pathophysiologic substrates involved in both disorders. Synapses as basic functional units of the brain are continuously modified by experience throughout life, therefore they are particularly attractive candidates for targeted therapy. Until recently we lacked a system to evaluate dynamic changes that lead to synaptic abnormalities. With the development of techniques to generate induced pluripotent stem cells (iPSCs) from patients, we are now able to study neuronal and synaptic development in cells from individual patients in the context of genetic changes conferring disease susceptibility. In this review, we discuss recent studies focusing on neural cells differentiated from SCZ and ASD patient iPSCs. These studies support a central role for glutamatergic synapse formation and function in both disorders and demonstrate that iPSC derived neurons offer a potential system for further evaluation of processes leading to synaptic dysregulation and for the design and screening of future therapies.
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