Journal Article

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

Zhang, Xiao, Jiang, Xuliang, Chen, Xuemei, Su, Diansan, Tian, Weitian, Yu, Weifeng, Huang, Lili, Tian, Jie, Gu, Xiyao

2018

Overview

Background Postoperative 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. Method Tibial 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). Results We 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. Conclusion These results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved. Anesthesia/surgery leads to working memory deficits in adult mice but has no effect on spatial reference memory. Central cholinergic system impairment might be the main reason for postoperative working memory deficits in adult mice.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Acetylcholinesterase - metabolism / Anesthesia / anesthesia/surgery / Anesthetics, Inhalation - toxicity / Animals / central cholinergic system / Choline O-Acetyltransferase - metabolism / Cholinergic Agents - pharmacology / Cholinesterase Inhibitors - pharmacology / Donepezil - pharmacology / Frontal Lobe - drug effects / Isoflurane - toxicity / Male / Maze Learning - drug effects / Memory / Memory Disorders - chemically induced / Memory Disorders - metabolism / Memory, Short-Term - drug effects / Mice, Inbred C57BL / Non-Neuronal Cholinergic System - physiology / Original Research / Proteins / Rodents / Spatial Memory - drug effects / Surgery / working memory