Long noncoding RNA SNHG16 reduced ketamine-induced neurotoxicity in human embryonic stem cell-derived neurons

Abstract

BackgroundClinical 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. MethodsHESCs 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. Results48-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. ConclusionsSNHG16 is an important epigenetic factor which may functionally modulate ketamine-induced neurotoxicity through NeuroD1.