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Eur J Pharmacol. 2019 Feb 5;844:56-64. doi: 10.1016/j.ejphar.2018.11.035. Epub 2018 Nov 28.

Inhibition of microRNA-375 ameliorated ketamine-induced neurotoxicity in human embryonic stem cell derived neurons.

Author information

1
Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054 Shaanxi, China.
2
Department of Clinical Laboratory, Xi'an NO. 3 Hospital, Xi'an, Shaanxi, 710018, China.
3
Department of Pathology, Beijing Key Laboratory of Translational Research on Neurodegenerative Diseases' Biomarkers, Peking University Third Hospital, Beijing 100091, China.
4
Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054 Shaanxi, China. Electronic address: doctorlhg@aol.com.

Abstract

Excessive exposure to commonly used anesthetic agents, such as ketamine, may induce permanent damage to immature human brains. In this work, we used a human embryonic stem cell (hESC)-derived neuron model to assess the expression and function of human microRNA 735 (hsa-miR-375) in regulating ketamine-induced neural cell death and neural toxicity in vitro. In the in vitro culture, hESC-derived neurons were incubated with ketamine for 72 h. After that, cell viability, reactive oxygen species activity, neural apoptosis, neurite degeneration, and hsa-miR-375 gene expression were assessed, respectively. We found ketamine induced neural death, reactive oxygen species augmentation, neural apoptosis, neurite degeneration and hsa-miR-375 upregulation, in hESC-derived neurons. In addition, we discovered that, lentivirus-mediated mR-375 downregulation protected ketamine-induced neural cell death and neural toxicity. Also, human brain derived neurotrophic factor (BDNF) was found to be directly and reversely regulated by hsa-miR-375. Moreover, BDNF downregulation was shown to functionally reverse the protective effect of miR-375 downregulation on ketamine-induced neural cell death and neural toxicity. Overall, this work provided strong evidence showing hsa-miR-375 is an active regulator in anesthesia-induced neural cell death and neural toxicity, possibly via inverse regulation on BDNF gene.

KEYWORDS:

Anesthesia; BDNF; Embryonic stem cell; Neural toxicity; hsa-miR-375

PMID:
30500346
DOI:
10.1016/j.ejphar.2018.11.035
[Indexed for MEDLINE]

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