Abstract
Propofol is a frequently used intravenous anesthetic agent. The impairment caused by propofol on the neural system, especially the hippocampus, has been widely reported. However, the molecular mechanism underlying the effects of propofol on learning and memory functions in the hippocampus is still unclear. In the present study we performed lncRNA and mRNA analysis in the hippocampi of adult mice, after propofol sedation, through RNA-Sequencing (RNA-Seq). A total of 146 differentially expressed lncRNAs and 1103 mRNAs were identified. Bioinformatics analysis, including gene ontology (GO) analysis, pathway analysis and network analysis, were done for the identified dysregulated genes. Pathway analysis indicated that the FoxO signaling pathway played an important role in the effects of propofol on the hippocampus. Finally, four lncRNAs and three proteins were selected from the FoxO-related network for further validation. The up-regulation of lncE230001N04Rik and the down-regulation of lncRP23-430H21.1 and lncB230206L02Rik showed the same fold change tendencies but changes in Gm26532 were not statistically significant in the RNA-Seq results, following propofol sedation. The FoxO pathway-related proteins, PI3K and AKT, are up-regulated in propofol-exposed group. FoxO3a is down-regulated at both mRNA and protein levels. Our study reveals that propofol sedation can influence the expression of lncRNAs and mRNAs in the hippocampus, and bioinformatics analysis have identified key biological processes and pathways associated with propofol sedation. Cumulatively, our results provide a framework for further study on the role of lncRNAs in propofol-induced or -related neurotoxicity, particularly with regards to hippocampus-related dysfunction.
Highlights
Propofol, the most widely used intravenous anesthetic agent in medical practice (Moseley et al, 1988), is noted among its analogs for its shorter onset and better recovery quality
We found that 6 h of propofol sedation impaired spatial learning and memory abilities in mice, determined by the Morris Water Maze (MWM) test
Bioinformatic analysis, including gene ontology (GO) analysis, pathway analysis, and network analysis suggested that the FoxO signaling pathway played an important role in the effect of propofol on the hippocampus
Summary
The most widely used intravenous anesthetic agent in medical practice (Moseley et al, 1988), is noted among its analogs for its shorter onset and better recovery quality. Over the past few decades, several researchers have reported its protective effects in ischemic-reperfusion injury, including cerebral ischemic injury. Some of these reports suggest that propofol’s neurotoxicity impairs hippocampus-related learning and memory functions (Vutskits et al, 2005; Erasso et al, 2013; Krzisch et al, 2013; Liu et al, 2017; Qiao et al, 2017; Yan et al, 2017). A recently reported study suggested that propofol induces an increase in TNF-α, short- or long-term neuronal apoptosis, neuronal loss, and synaptic loss (Chen et al, 2016). The role of long non-coding RNA (lncRNA) in propofol-induced neurotoxicity, in the hippocampus, is still unknown
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