Central cholinergic system mediates working memory deficit induced by anesthesia/surgery in adult mice

Abstract

BackgroundPostoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although POCD occurs mainly in aged patients, it happens at any age. Previous studies demonstrated that anesthesia/surgery had no effects on reference memory of adult mice. However, whether it impairs working memory remains unclear. Working memory deficit would result in many deficits of executive function. We hypothesized that anesthesia/surgery impaired the working memory of adult mice and the central cholinergic system was involved.MethodTibial fracture internal fixation under the anesthesia of isoflurane was performed in two‐month‐old C57BL/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (MWM). Donepezil, an inhibitor of acetylcholinesterase (AChE), was administered in another cohort mice for 4 weeks. Then, the working memory was measured by MWM 2 days after anesthesia/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (ChAT), AChE, vesicular acetylcholine transporter (VAChT), and choline transporter (ChT) in the prefrontal cortex (PFC).ResultsWe found that anesthesia/surgery had no effects on the reference memory, but it impaired the working memory in adult mice. Meanwhile, we also found that the protein level of ChAT in PFC decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of ChAT induced by anesthesia/surgery.ConclusionThese results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved.

Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice

“…We did not investigate how other domains of learning and memory such as working memory changed after multiple anesthesia/surgery. In our previous study, we demonstrated that although the spatial reference memory was not changed after a single anesthesia/surgery, the working memory was impaired in young adult mice [33]. Although exposure to multiple anesthesia/surgery in such a short period is not common in clinical practice, our data from the present study indicated that the effects of multiple anesthesia/surgery on learning and memory are no worse than those of a single anesthesia/surgery.…”

“…The central cholinergic system is essential for learning and memory, including the modulation of the acquisition, encoding, consolidation, reconsolidation, extinction, and retrieval of memory [32]. Our previous work showed that central cholinergic neuronal degeneration facilitates the development of POCD [10,33]. In this study, the central cholinergic system was stable after multiple anesthesia/surgery, corresponding to normal learning and memory.…”

Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice

“…The use of AChE inhibitors elevates the concentration of acetylcholine in treated tissues, and can have the ability to enhance cognitive performance (Brousseau et al, 2007 ). A recent study has shown that donepezil could reverse cognitive impairments in aged rodents subjected to anesthesia and surgery (Zhang et al, 2018 ). Moreover, there are many clinical trials evaluating the effects of FDA-approved AChE inhibitors, such as rivastigmine and donepezil, on the prevention and treatment of POCD 1 .…”

A Mouse Model of Hepatic Ischemia-Reperfusion Injury Demonstrates Potentially Reversible Effects on Hippocampal Neurons and Postoperative Cognitive Function

“…Lu et al found relatively higher ChAT activity and choline intake in rats during the MWM task [22]. Zhang et al performed anesthesia and surgery on rats and found that memory deficit was associated with defects in the central cholinergic system [23]. Therefore, in this study, the expression of ChAT in the mouse hippocampus was studied to determine whether its expression could reflect the effect of hepatic ischemia-reperfusion injury on cognitive function.…”