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Front Neurol. 2017 Dec 07;8:626. doi: 10.3389/fneur.2017.00626. eCollection 2017.

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

Frontiers in neurology

Jing Huang, Fangkun Liu, Hui Tang, Haishan Wu, Lehua Li, Renrong Wu, Jingping Zhao, Ying Wu, Zhixiong Liu, Jindong Chen

Affiliations

  1. Department of Psychiatry, The Second Xiangya Hospital, Central South University (CSU), Changsha, China.
  2. 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.
  3. Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, China.
  4. Intensive Care Unit, The Second Xiangya Hospital, Central South University (CSU), Changsha, China.

PMID: 29270148 PMCID: PMC5725435 DOI: 10.3389/fneur.2017.00626

Abstract

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

Keywords: cerebral organoids; in vitro models; neuropsychiatric disease; neurotoxicity; tranylcypromine

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