Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction

Xu, Huan; Chen, Lingke; Zhang, Xiao; Jiang, Xuliang; Tian, Weitian; Yu, Weifeng; Wang, Xiangrui; Tian, Jie; Su, Diansan

doi:10.1038/s41374-018-0174-9

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…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.…”

Section: Discussionsupporting

confidence: 48%

“…Lin and Zuo demonstrated that 4-month-old male rats exposed to isoflurane had significant impairments in longterm spatial memory assessed using a Barnes maze in addition to impaired hippocampus-dependent learning and memory in a fear conditioning test [9]. However, our previous work showed that single anesthesia/surgery induced memory decline and attenuated central cholinergic biomarkers in aged mice but not in adult mice [10]. Walters et al [11] demonstrated that exposure to anesthesia alone does not cause persistent learning and memory impairments in adult monkeys.…”

Section: Introductionmentioning

confidence: 85%

“…Cholinergic System. We have previously demonstrated that central cholinergic neuronal degeneration promotes the development of POCD in aged mice [10]. Does multiple anesthesia/surgery affect the central cholinergic system?…”

Section: Multiple Anesthesia/surgery Did Not Impair the Centralmentioning

confidence: 99%

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Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice

Zhou

et al. 2020

Mediators of Inflammation

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Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients. Numerous studies have demonstrated that multiple surgery/anesthesia during the neurodevelopmental period affects cognitive function, whereas a single anesthesia/surgery rarely causes cognitive dysfunction in adults. However, whether adults who undergo multiple anesthesia/surgery over a short period will experience cognitive dysfunction remains unclear. In this study, central nervous system inflammation and changes in cholinergic markers were investigated in adult mice subjected to multiple laparotomy procedures over a short period of time. The results showed that despite the increased expression of IL-6 and TNF-α in the hippocampus after multiple operations and the activation of microglia, multiple anesthesia/surgery did not cause a decline in cognitive function in adult mice. There were no changes in the cholinergic markers after multiple anesthesia/surgery.

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Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 85%

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Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice

Zhou

et al. 2020

Mediators of Inflammation

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“…Studies have found that after 40 years old, the central cholinergic neurons of human beings begin to degenerate. Different individuals have different degrees of degeneration [ 25 ]. At the same time, a study has shown that degeneration of the central cholinergic nervous system will lead to the occurrence of AD, and CSF analysis has confirmed that the elderly with AD will have increased risk of POD [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Tang

Liu

et al. 2020

BMC Anesthesiol

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Background Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. Methods Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. Results POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. Conclusion The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. Trial registration This study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

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“…Animals were sacrificed by decapitation, as described in our previous studies (Zhang et al, 2018;Xu et al, 2019). After transcardial perfusion with saline, the hippocampus was quickly dissected on ice, frozen in liquid nitrogen, and stored at −80 • C. Hippocampus tissues were homogenized in cold radioimmunoprecipitation assay buffer (Beyotime Biotechnology, China), and the quantity of protein in the supernatants was determined using a bicinchoninic acid protein assay kit (Thermo Fisher Scientific, Waltham, MA, United States).…”

Section: Western Blottingmentioning

confidence: 99%

Peripheral Neutrophils-Derived Matrix Metallopeptidase-9 Induces Postoperative Cognitive Dysfunction in Aged Mice

Huang

Tian

et al. 2022

Front. Aging Neurosci.

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BackgroundAging is one of the most important risk factors of postoperative cognitive dysfunction (POCD); however, the mechanisms are still not completely understood. In this study, we explore the roles of matrix metalloproteinase-9 (MMP-9) in aged mice with POCD.MethodsAppendectomy was performed in 18-month-old C57BL/6 and MMP-9–/– mice under anesthesia to establish the POCD model. Learning and memory were assessed using the Morris water maze (MWM) or Barnes maze. Protein expression of MMP-9 was measured by Western blotting or enzyme-linked immunosorbent assay (ELISA). To explore the role of neutrophils-derived MMP-9 in POCD, we treated mice with anti-Gr-1 monoclonal antibody to deplete peripheral neutrophils. And the percentage of neutrophils and other leukocytes were detected by flow cytometry. We further used sodium fluorescein (NaFlu) to evaluate the blood–brain barrier (BBB) permeability.ResultsThe spatial learning and memory ability was injured, and expression of MMP-9 increased in both plasma and the hippocampus after anesthesia/surgery. However, cognitive dysfunction was alleviated in both MMP-9–/– and peripheral neutrophils-depleted mice. The permeability of BBB was increased after anesthesia/surgery while recused by anti-Gr-1 antibody administration.ConclusionThese findings suggest that peripheral neutrophils-derived MMP-9 could lead to POCD of aged mice through increasing the BBB permeability.

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Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction

Cited by 26 publications

References 44 publications

Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice

Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Peripheral Neutrophils-Derived Matrix Metallopeptidase-9 Induces Postoperative Cognitive Dysfunction in Aged Mice

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