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在体模拟精神分裂症:研究脑细胞的挑战与启示。

Modeling Schizophrenia In Vitro: Challenges and Insights on Studying Brain Cells.

机构信息

Laboratory of Neuroproteomics, Department of Cell and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, São Paulo, Brazil.

出版信息

Adv Exp Med Biol. 2022;1400:35-51. doi: 10.1007/978-3-030-97182-3_3.

Abstract

One of the challenges in studying neuropsychiatric disorders is the difficulty in accessing brain tissue from living patients. Schizophrenia is a chronic mental illness that affects 1% of the population worldwide, and its development stems from genetic and environmental factors. In order to better understand the pathophysiology underlying schizophrenia, the development of efficient in vitro methods to model this disorder has been required. In addition to several in vitro models, induced pluripotent stem cells (iPSCs) arose as a powerful tool, enabling access to the genetic background of the donor. Moreover, genetic modification of these cells can improve studies of specific dysfunctions observed in the pathophysiology of several neuropsychiatric disorders, not only schizophrenia. Here, we summarize which in vitro models are currently available and their applications in schizophrenia research, describing their advantages and limitations. These technologies in the cell culture field hold great potential to contribute to a better understanding of the pathophysiology of schizophrenia in an integrated manner, in addition to testing potential therapeutic interventions based on the genetic background of the patient.

摘要

研究神经精神疾病的挑战之一是难以从活体患者获取脑组织。精神分裂症是一种影响全球 1%人口的慢性精神疾病,其发展源于遗传和环境因素。为了更好地理解精神分裂症的病理生理学基础,需要开发有效的体外方法来对此疾病进行建模。除了几种体外模型外,诱导多能干细胞(iPSC)的出现成为了一种强大的工具,使人们能够访问供体的遗传背景。此外,对这些细胞进行基因修饰可以改善对几种神经精神疾病病理生理学中观察到的特定功能障碍的研究,不仅是精神分裂症。在这里,我们总结了目前可用的体外模型及其在精神分裂症研究中的应用,描述了它们的优点和局限性。这些细胞培养领域的技术具有很大的潜力,可以在综合的基础上促进对精神分裂症病理生理学的更好理解,此外还可以基于患者的遗传背景来测试潜在的治疗干预措施。

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