MicroRNAs: New Players in Anesthetic-Induced Developmental Neurotoxicity.

Twaroski D Bosnjak Zj

doi:10.4172/2153-2435.1000357

Abstract

Growing evidence demonstrates that prolonged exposure to general anesthetics during brain development induces widespread neuronal cell death followed by long-term memory and learning disabilities in animal models. These studies have raised serious concerns about the safety of anesthetic use in pregnant women and young children. However, the underlying mechanisms of anesthetic-induced neurotoxicity are complex and are not well understood. MicroRNAs are endogenous, small, non-coding RNAs that have been implicated to play important roles in many different disease processes by negatively regulating target gene expression. A possible role for microRNAs in anesthetic-induced developmental neurotoxicity has recently been identified, suggesting that microRNA-based signaling might be a novel target for preventing the neurotoxicity. Here we provide an overview of anesthetic-induced developmental neurotoxicity and focus on the role of microRNAs in the neurotoxicity observed in both human stem cell-derived neuron and animal models. Aberrant expression of some microRNAs has been shown to be involved in anesthetic-induced developmental neurotoxicity, revealing the potential of microRNAs as therapeutic or preventive targets against the toxicity.

Highlights

In 1979, Steen and Michenfelder compiled several clinical case studies into a review article and highlighted the possible issue of anesthetic-induced neurotoxicity [1]
Neonatal mice miR-34c miR-34c was upregulated in the hippocampus of neonatal mice exposed to ketamine and downregulation of miR-34c attenuated the ketamine-induced neuronal cell death and cognitive impairment
MiR-124 was upregulated in the hippocampus of neonatal mice exposed to ketamine and knockdown of miR-124 reduced ketamine-induced apoptosis in hippocampal CA1 neurons in vitro and activated the protein kinase C (PKC)-extracellular-signal regulated kinase (ERK) pathway. miR-124 knockdown improved memory performance of mice treated with ketamine

Summary

Introduction

In 1979, Steen and Michenfelder compiled several clinical case studies into a review article and highlighted the possible issue of anesthetic-induced neurotoxicity [1]. Several studies done in developing rodent models found that most anesthetics including isoflurane, sevoflurane, ketamine, propofol and anesthetic combinations could induce cell death in the brains of these animals and lead to learning and memory impairments later in life [9,10,11,12,13]. The findings from these studies suggested that anesthetics could both directly and indirectly induce neuronal cell death in the developing brain.

Results

Conclusion