The recovery from transient cognitive dysfunction induced by propofol was associated with enhanced autophagic flux in normal healthy adult mice

Abstract

Propofol is the most widely accepted intravenous anesthetic available for clinical use. However, neurotoxicity of propofol in the developing brain has been reported. This study investigated the effects of propofol on cognitive function in normal healthy adult mice. Thirty-three GFP-LC3 adult mice were included. Propofol was injected for anesthesia (n = 22). The sham control (n = 11) received intralipid injections. The mice completed a Y-maze test on 3 and 7 days after being anesthetized. Western blotting, immunofluorescence staining, and transmission electron microscopic (TEM) analyses were performed with their hippocampi. In addition, we conducted a separate ex vivo experiment using organotypic hippocampal slice cultures (OHSCs) to investigate the effects of propofol on induced autophagy. There was a significantly lower percentage of alternation in the Y-maze test on day 3 after propofol anesthesia than the control, but no difference was observed on day 7. Western blot analyses and immunofluorescence assays showed that the levels of cognitive function-related proteins significantly decreased in the propofol group compared to the control on day 3 but had recovered by day 7. In terms of autophagy-related proteins, western blot analyses and immunofluorescence assays showed that propofol increased autophagic induction, flux, and degradation of autophagosomes. Ex vivo experiments showed that propofol enhanced autophagic flux of the induced autophagy. In conclusion, although transient cognitive dysfunction occurred, adult mice recovered their cognitive function after the administration of propofol anesthesia. And this finding may be associated with enhanced autophagic flux.