Neonatal anesthesia exposure impacts brain microRNAs and their associated neurodevelopmental processes

Abstract

MicroRNAs (miRNAs), when subjected to environmental stimuli, can exhibit differential expression. As critical regulators of gene expression, differential miRNA expression has been implicated in numerous disorders of the nervous system. In this study, we focused on the effect of a general anesthetic, as an environmental stimulus, on miRNA expression of the developing brain. General anesthetics have potential long-lasting neurotoxic effects on the developing brain, resulting in behavioral changes in adulthood. We first carried out an unbiased profiling approach to examine the effect of single-episode neonatal general anesthetic, sevoflurance (sevo), exposure on miRNA expression of the brain. Neonatal sevo has a significant effect on the expression of specific miRNAs of the whole brain and the hippocampus that is both immediate – directly after neonatal treatment, as well as long-lasting - during adulthood. Functionally, neonatal sevo-associated miRNA gene-targets share potential neurodevelopmental pathways related to axon guidance, DNA transcription, protein phosphorylation and nervous system development. Our understanding on the role of miRNAs provides a putative epigenetic/molecular bridge that links neonatal general anesthetic’s effect with its associated functional change.

Neonatal sevoflurane exposure induces long-term changes in dendritic morphology in juvenile rats and mice

“…Therefore, anesthesia exposure is expected to influence gene expression at least acutely over the duration of anesthetic action. 59,60 But if the brain is exposed to anesthetics during sensitive periods of neurodevelopment -particularly synaptogenesis -the effects of anesthetics on neuronal gene expression appear to be chronic. 28,61 Dysregulation caused by neonatal anesthesia exposure encompasses an array of genes that themselves regulate the transcriptional activity of other genes (Crem, Creb1, CREBBP), 29 that serve as activity-dependent immediate early genes (Arc, junB, c-Fos), 29,30 and that control neuronal survival and morphology (Brainderived neurotrophic factor [BDNF], synaptophysin, drebrin, [24,53]).…”

The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

“…In the recent years, many studies have focused on the roles of this post-transcriptional modification in the neonatal GA-induced prolong cognitive dysfunction ( Figure 1 ). Lin et al (2018a) carried out a comprehensive unbiased profile assay that revealed the effects of neonatal sevoflurane exposure on miRNA expression of the brain. The data shows that the neonatal sevoflurane had significant impact on the expression of specific miRNAs, and this GA-induced changes have region and time specificity.…”