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重编程细胞是研究精神障碍中多巴胺功能障碍的有用工具吗?当前证据综述。

Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence.

作者信息

Sauerzopf Ulrich, Sacco Roberto, Novarino Gaia, Niello Marco, Weidenauer Ana, Praschak-Rieder Nicole, Sitte Harald, Willeit Matthäus

机构信息

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Institute of Science and Technology Austria, Klosterneuburg, Austria.

出版信息

Eur J Neurosci. 2017 Jan;45(1):45-57. doi: 10.1111/ejn.13418. Epub 2016 Oct 19.

Abstract

Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.

摘要

自2006年以来,重编程细胞除了在神经精神疾病研究方法中应用外,越来越多地被用作一种生物医学研究技术。这些快速发展的技术能够生成神经元亚群,不仅引发了对单基因神经精神疾病的兴趣,也激发了对多基因和多病因疾病如精神分裂症(SCZ)和双相情感障碍(BPD)的研究热情。本综述总结了19篇关于源自SCZ患者的重编程成体细胞的出版物,以及5篇在BPD患者中使用该技术的出版物。由于这两种疾病都复杂且具有异质性,因此有多个假设需要在体外进行验证。在SCZ中,尽管所谓的SCZ多巴胺假说具有很强的解释力,但关于体外多巴胺能传递改变的数据却很少。一些研究结果与细胞能量代谢紊乱有关,重编程细胞中的观察结果表明存在神经发育改变。一些研究还报告了药物化合物在逆转细胞模型中观察到的改变方面的疗效。然而,由于重复研究较少,目前使用重编程细胞的研究无法得出全面的结论。未来,细胞培养方法的研究结果需要与临床、流行病学、药理学和影像学数据相结合,以便更全面地了解SCZ和BPD。

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