Propofol Induces Postoperative Depression and Inhibits Microglial Function in Mice

Abstract

Many patients experience excellent physical recoveries after surgery; however, there are some of them who from suffer mood fluctuation, even depression. Postoperative depression may be resulted from cognitive dysfunction, pain, and a compromised immune system during the surgery. But there is a higher possibility that general anaesthesia may be responsible for the development of depression. Here, we employed one of the most used anaesthetics, propofol, in a mouse model to investigate whether this intravenous anaesthetic compound could cause depressive-like behavioural performance in mice. We found a single dose of propofol caused significant abnormal behavioural performance in tail suspension, forced swimming, and open field tests. We also examined the brain section of these mice and revealed that there was significant reduced expression of the CD11b protein, which demonstrated an inhibition of propofol on microglial function. We investigated the effect of propofol on synaptic protein, SYP, and found there was no notable influence on the protein expression. These above results suggested that propofol treatment might promote the depressive-like behaviours in mice via influencing the microglial cell function. Furthermore, we found the level of the IL-6 cytokine was significantly increased in the brain tissue, which might subsequently cause the activation of the transcriptional factor, STAT3. Our finding may provide a new perspective of further understanding the mechanism of anaesthetic drugs and deciphering the underlying mechanism of postoperative depression.

The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours

“…In contrast, Wu et al 11 found potentially beneficial effects of propofol in reducing microglial inflammation through NMDA receptor inhibition. Nevertheless, taken together, the study by Feng et al 38 and ours are consistent with the notion that a single dose of propofol in C57BL/6 mice does not have enduring antidepressant-like effects.…”

“…In contrast, our mice and Feng's mice were not subjected to stress or depressive model preconditioning. 38 This may have been a factor in the lack of a salutary effect of propofol on immobility time in our study as well as the study by Feng et al 38 …”

“…10 , 37 However, the behavioral, cognitive, neurophysiological and synaptic plasticity effects of propofol, ketamine, and brexanolone and other anesthetic agents have been reported to persist in rodents and humans substantially longer than would be anticipated by their pharmacokinetic and pharmacodynamic profiles alone. 2 , 4 , 11 , 17 , 26 , 27 , 33 , 34 , 38 , 39 , 40 , 41 For example, in their review, Browne and Lucki 41 observed that “the majority of studies indicate that the FST remains sensitive to the protracted effects of ketamine up to 1 week after a single injection.” Thus, the rapid clearance of propofol is unlikely to explain the lack of influence on an FST at 24 hours.…”

“…Feng et al 38 reported that a single dose of propofol 75 mg/kg IP statistically significantly shortened struggling time in the FST and tail suspension test, reduced expression of CD11b and increased expression of p-STAT-3 in the brain tissues of C57BL/6 mice. They speculated that the decreased struggling time might have been mediated by interference in microglial function stemming from these brain tissue changes.…”

The Role of Microglia in Perioperative Neurocognitive Disorders

“…But propofol, a widely used intravenous anesthetic, has no effects on neuroinflammation and cognition in the Alzheimer’s transgenic model (Mardini et al, 2017 ). Another study showed that propofol-induced postoperative depressive-like behaviors, which is attributed to the inhibition of microglial activation (Song et al, 2019 ). in vitro studies show propofol has neuroprotective effects by attenuating inflammatory response in microglia (Gui et al, 2012 ; Peng et al, 2014 ).…”