General Anaesthetic Modulation of Memory-Related Gene Expression in the Cerebral Cortex

Abstract

General anaesthetics have been widely used in a clinical setting, having remained one of the most important drugs in medicine for their role in enabling major surgical procedures to be carried out. One of the fundamental outcomes of an anaesthetic is amnesia, as this prevents patient recall of events surrounding surgery. The hippocampal region of the mammalian brain has been investigated for its role in memory formation, however the cerebral cortex also has recognised importance in memory consolidation and storage processes. General anaesthetics cause widespread neurochemical changes in the brain and the disruption to memory consolidation processes is likely to involve alteration to the expression patterns of memory-related genes. The aim of this research was to investigate the cerebrocortical gene expression pattern of five memory-related genes, Arc, Bdnf, CaMKIIα, Gjd2 and Grin1 during exposure to anaesthesia induced by sevoflurane, isoflurane and propofol. Real-time quantitative PCR (qPCR) was used to analyse expression of the individual mRNA transcripts and REST© software was used to carry out statistical analysis of the mRNA expression of each gene of interest. Our research demonstrated that Bdnf was significantly down-regulated by sevoflurane at t=2 hours and t=4 hours and propofol at t=2 hours (p<0.05). Up-regulation of Arc after a four exposure to propofol was also observed but no change in Arc was found at the other time points. There was no change in the expression of CaMKIIα, Gjd2 or Grin1 during sevoflurane- or propofol- induced anaesthesia. We recommend analysis of other Bdnf transcript variants in the mouse brain during anaesthesia, as well as levels of the BDNF protein to further validate these results.