Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00626/full |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jing Huang Jing Huang Fangkun Liu Hui Tang Hui Tang Haishan Wu Haishan Wu Lehua Li Lehua Li Renrong Wu Renrong Wu Jingping Zhao Jingping Zhao Ying Wu Zhixiong Liu Jindong Chen Jindong Chen |
| spellingShingle |
Jing Huang Jing Huang Fangkun Liu Hui Tang Hui Tang Haishan Wu Haishan Wu Lehua Li Lehua Li Renrong Wu Renrong Wu Jingping Zhao Jingping Zhao Ying Wu Zhixiong Liu Jindong Chen Jindong Chen Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model Frontiers in Neurology cerebral organoids tranylcypromine neurotoxicity in vitro models neuropsychiatric disease |
| author_facet |
Jing Huang Jing Huang Fangkun Liu Hui Tang Hui Tang Haishan Wu Haishan Wu Lehua Li Lehua Li Renrong Wu Renrong Wu Jingping Zhao Jingping Zhao Ying Wu Zhixiong Liu Jindong Chen Jindong Chen |
| author_sort |
Jing Huang |
| title |
Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model |
| title_short |
Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model |
| title_full |
Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model |
| title_fullStr |
Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model |
| title_full_unstemmed |
Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model |
| title_sort |
tranylcypromine causes neurotoxicity and represses bhc110/lsd1 in human-induced pluripotent stem cell-derived cerebral organoids model |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Neurology |
| issn |
1664-2295 |
| publishDate |
2017-12-01 |
| description |
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. |
| topic |
cerebral organoids tranylcypromine neurotoxicity in vitro models neuropsychiatric disease |
| url |
http://journal.frontiersin.org/article/10.3389/fneur.2017.00626/full |
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1725789520489611264 |
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doaj-d9b03dd512464be894b1b7188335276b2020-11-24T22:16:30ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-12-01810.3389/fneur.2017.00626280971Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids ModelJing Huang0Jing Huang1Fangkun Liu2Hui Tang3Hui Tang4Haishan Wu5Haishan Wu6Lehua Li7Lehua Li8Renrong Wu9Renrong Wu10Jingping Zhao11Jingping Zhao12Ying Wu13Zhixiong Liu14Jindong Chen15Jindong Chen16Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaIntensive Care Unit, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, ChinaMental Health Institute of the Second Xiangya Hospital, Chinese National Technology Institute on Mental Disorders, Central South University (CSU), Chinese National Clinical Research Center on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, ChinaRecent 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.http://journal.frontiersin.org/article/10.3389/fneur.2017.00626/fullcerebral organoidstranylcypromineneurotoxicityin vitro modelsneuropsychiatric disease |