{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:20:58Z","timestamp":1777418458095,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T00:00:00Z","timestamp":1521763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571030"],"award-info":[{"award-number":["81571030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771133"],"award-info":[{"award-number":["81771133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["YG2017MS53"],"award-info":[{"award-number":["YG2017MS53"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Postoperative cognitive dysfunction (<jats:styled-content style=\"fixed-case\">POCD<\/jats:styled-content>) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although <jats:styled-content style=\"fixed-case\">POCD<\/jats:styled-content> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Tibial fracture internal fixation under the anesthesia of isoflurane was performed in two\u2010month\u2010old C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (<jats:styled-content style=\"fixed-case\">MWM<\/jats:styled-content>). Donepezil, an inhibitor of acetylcholinesterase (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>hE), was administered in another cohort mice for 4\u00a0weeks. Then, the working memory was measured by <jats:styled-content style=\"fixed-case\">MWM<\/jats:styled-content> 2\u00a0days after anesthesia\/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>hE, vesicular acetylcholine transporter (<jats:styled-content style=\"fixed-case\">VAC<\/jats:styled-content>hT), and choline transporter (ChT) in the prefrontal cortex (<jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> induced by anesthesia\/surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that anesthesia\/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.957","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T20:20:30Z","timestamp":1521836430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Central cholinergic system mediates working memory deficit induced by anesthesia\/surgery in adult mice"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuliang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weitian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiyao","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-1025","authenticated-orcid":false,"given":"Diansan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.218610"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/y86-061"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1308\/rcsann.2016.0338"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000055871.82308.41"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100825"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000266627.96040.5a"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.10.2074"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35050103"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22082"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022219412455238"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.02.022"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/desc.12068"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318286d0c9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91229"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X13666150716165726"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.53841\/bpsecp.2003.20.3.109","article-title":"Working memory assessments at school entry as longitudinal predictors of National Curriculum attainment levels","volume":"20","author":"Gathercole S. 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