title: Long noncoding RNA BDNF-AS regulates ketamine-induced neurotoxicity in neural stem cell derived neurons.
abstract: BACKGROUND
  Ketamine is an anesthetic commonly used in both humans and animals. Emerging evidence has demonstrated that ketamine may induce neurotoxicity in neural stem cell-derived neurons. In this work, we investigated whether long noncoding RNA (lncRNA) Brain derived neurotrophic factor antisense (BDNF-AS) was involved in ketamine-induced neurotoxicity in differentiation of mouse embryonic neural stem cells.
  
  
  METHODS
  Mouse embryonic neural stem cells were differentiated in vitro, and treated with ketamine. The corresponding change in gene expression levels of BDNF and BDNF-AS were assessed by qRT-PCR. BDNF-AS was subsequently downregulated by siRNA. And its effect on protecting neuronal apoptosis, promoting neurite regrowth, and activating TrkB signaling pathways were assessed by TUNEL assay, neurite outgrowth assay, and western blot assay, respectively.
  
  
  RESULTS
  In ketamine-injured mouse embryonic neural stem cell-derived neurons, BDNF was downregulated, whereas BDNF-AS was upregulated in dose-dependent manner. SiRNA-mediated BDNF-AS downregulation ameliorated neuronal apoptosis, induced neurite outgrowth, and phosphorylated TrkB signaling pathway after ketamine-induce neurotoxicity in mouse embryonic neural stem cell-derived neurons.
  
  
  CONCLUSIONS
  Inhibition of BDNF-AS is a novel method to protect ketamine-induced neurotoxicity in mouse embryonic neural stem cell-derived neurons, very likely through the activation of TrkB signaling pathway.
authors.affiliation: Department of anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of anesthesiology, Zhejiang Hospital, Hangzhou, 310002, China.
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: lcs6678@aol.com.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of anesthesiology, Shaoxing Pepople's Hospital, Shaoxing, 312300, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of anesthesiology, Zhejiang Hospital, Hangzhou, 310002, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007649:Ketamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D062085:RNA, Long Noncoding / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009498:Neurotoxins; D062085:RNA, Long Noncoding; C000613900:long noncoding RNA BDNF-AS, mouse; D007649:Ketamine; D020813:Receptor, trkB
keywords: BDNF-AS; Ketamine; Neural stem cell; Neurotoxicity; lncRNA