Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

被引：25

作者：

Huang, Jing ^{[1
,2
]}

Liu, Fangkun ^{[3
]}

Tang, Hui ^{[1
,2
]}

Wu, Haishan ^{[1
,2
]}

Li, Lehua ^{[1
,2
]}

Wu, Renrong ^{[1
,2
]}

Zhao, Jingping ^{[1
,2
]}

Wu, Ying ^{[4
]}

Liu, Zhixiong ^{[3
]}

Chen, Jindong ^{[1
,2
]}

机构：

[1] Cent S Univ, Xiangya Hosp 2, Dept Psychiat, Changsha, Hunan, Peoples R China

[2] Cent S Univ, Chinese Natl Clin Res Ctr Mental Disorders, Hunan Key Lab Psychiat & Mental Hlth, Mental Hlth Inst,Xiangya Hosp 2,Chinese Natl Techn, Changsha, Hunan, Peoples R China

[3] Cent S Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Hunan, Peoples R China

[4] Cent S Univ, Xiangya Hosp 2, Intens Care Unit, Changshu, Jiangsu, Peoples R China

来源：

FRONTIERS IN NEUROLOGY | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

cerebral organoids; tranylcypromine; neurotoxicity; in vitro models; neuropsychiatric disease; MONOAMINE-OXIDASE INHIBITORS; 3-DIMENSIONAL CULTURE; BRAIN; DEMETHYLATION; CHALLENGES; GENERATION; DEPRESSION; DISORDERS; COMPLEXES; LSD1;

D O I：

10.3389/fneur.2017.00626

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Recent breakthroughs in human pluripotent stem cell-derived cerebral organoids provide a valuable platform for investigating the human brain after different drugs treatments and for understanding the complex genetic background to human pathology. Here, we identified tranylcypromine, which is used to treat refractory depression, caused human-induced pluripotent stem cell-derived brain organoids neurotoxicity, leading to decreased proliferation activity and apoptosis induction. Moreover, tranylcypromine treatment affects neurons and astrocytes, which impairs cell density and arrangement. Finally, staining of histone demethylation-related genes revealed that tranylcypromine suppresses the transcriptional activity of BHC110/LSD1-targeted genes and increases the expression of histone di-methylated K4. These results show that human brain organoids can be applied as an in vitro model for CNS drug screening to evaluate structural, cellular, and molecular changes in the normal brains or brains of patients with neuropsychiatric disorders after drug treatments.

引用

页数：9

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