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

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

doi:10.3389/fneur.2017.00626

Frontiers in Neurology (Dec 2017)

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

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

Affiliations

Jing Huang: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Jing Huang: Mental 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, China
Fangkun Liu: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, China
Hui Tang: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Hui Tang: Mental 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, China
Haishan Wu: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Haishan Wu: Mental 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, China
Lehua Li: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Lehua Li: Mental 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, China
Renrong Wu: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Renrong Wu: Mental 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, China
Jingping Zhao: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Jingping Zhao: Mental 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, China
Ying Wu: Intensive Care Unit, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Zhixiong Liu: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, China
Jindong Chen: Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China
Jindong Chen: Mental 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, China

DOI: https://doi.org/10.3389/fneur.2017.00626
Journal volume & issue: Vol. 8

Abstract

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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.

Published in Frontiers in Neurology

ISSN: 1664-2295 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.frontiersin.org/journals/neurology/

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