Ketamine induces neuronal apoptosis and cognitive disorder via miR-199a-5p/HIF-1α in neonatal rats

It reported that repeated administration of clinical doses of ketamine could induce neuronal apoptosis in the immature brain. In this study, Sprague-Dawley postnatal day 7 rats were treated with ketamine. As the rats grew, we found ketamine impaired the cognitive function of the rats. Ketamine increased HIF-1α level in the brain tissues of rats as compared to the control group and YC-1 rescued those effects. The escape latency and the platform crossing time of Morris water maze decreased in the YC-1-treated rats compared to the control in ketamine-treated rats. We also found that ketamine decreased the expression of miR-199a-5p and HIF-1α is a directly target of miR-199a-5p. Administration of ketamine also decrease the cell activity while YC-1 and MiR-199a-5p mimics rescued the inhibition effect. In conclusion, we suggest that ketamine-induced neuronal apoptosis in neonatal rats, followed by learning and memory impairment, might be mediated via the miR-199a-5p/HIF-1α signalling pathway.