Long noncoding RNA SNHG16 reduced ketamine-induced neurotoxicity in human embryonic stem cell-derived neurons.
Xiaochuan Pang, Zhenbo Su, Yanping Sun, Wenwen Zhang, Hushan Wang
Journal of chemical neuroanatomy December 2018 DOI: 10.1016/j.jchemneu.2018.08.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Human embryonic stem cell-derived neurons |
| Interventions | Ketamine SNHG16 overexpression |
| Duration | 48 h treatment |
| Topics | Ketamine Esketamine |
| Keywords | Neurod1 Neurotoxicity Snhg16 Lncrna |
| Key findings | Ketamine treatment for 48 hours induced neurotoxicity and downregulated SNHG16 in hESC-derived neurons. Overexpressing SNHG16 reduced ketamine-induced neurotoxicity, and this protection was reversed by siRNA-mediated knockdown of NeuroD1, which SNHG16 upregulated. The authors propose that SNHG16 modulates ketamine-induced neurotoxicity through NeuroD1. |
Abstract
Clinical evidence demonstrates that prolonged exposure to ketamine may cause irreversible injury to immature human brains. In this study, we utilized an in vitro model to examine the function of long noncoding RNA (lncRNA) SNHG16 in ketamine-induced neurotoxicity in human embryonic stem cell (hESC)-derived neurons. HESCs were induced toward neuronsin vitro, and treated with ketamine, at various concentrations, for 48 h. Viability, apoptosis, caspase-3 activity and ROS activity were then examined among hESC-derived neurons. Ketamine-induced gene expression change of SNHG16 was assessed by qRT-PCR. SNHG16 was overexpressed in hESC-derived neurons, which were then treated with ketamine, followed by biochemical assays to assess the effects of SNHG16 upregulation on ketamine-induced neurotoxicity. Correlation between SNHG16 and NeuroD1 gene was assess by qRT-PCR. In SNHG16-upregulated hESC-derived neurons, they were double transfected with siRNA to knock down NeuroD1. The functions of NeuroD1 inhibition on SNHG16-associated neural protection on ketamine-induced neurotoxicity were further assessed. 48-h in vitro treatment of ketamine induced significant neurotoxicity, and downregulated SNHG16 among hESC-derived neurons. Conversely, SNHG16 upregulation reduced ketamine-induced neurotoxicity. NeuroD1 expression was downregulated by ketamine in hESC-derived neurons, and concomitantly upregulated by SNHG16 overexpression. SiRNA-mediated NeuroD1 inhibition reversed the protection of SNHG16 upregulation on ketamine-induced neurotoxicity. SNHG16 is an important epigenetic factor which may functionally modulate ketamine-induced neurotoxicity through NeuroD1.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |