Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss

作者全名："Wang, Qing; Zhang, Xiang; Guo, Yu-Jie; Pang, Ya-Yan; Li, Jun-Jie; Zhao, Yan-Li; Wei, Jun-Fen; Zhu, Bai-Ting; Tang, Jing-Xiang; Jiang, Yang-Yang; Meng, Jie; Yue, Ji-Rong; Lei, Peng"

作者地址："[Wang, Qing; Zhang, Xiang; Guo, Yu-Jie; Zhao, Yan-Li; Wei, Jun-Fen; Zhu, Bai-Ting; Tang, Jing-Xiang; Jiang, Yang-Yang; Meng, Jie; Yue, Ji-Rong; Lei, Peng] Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Dept Geriatr, Chengdu 610041, Sichuan, Peoples R China; [Wang, Qing; Zhang, Xiang; Guo, Yu-Jie; Zhao, Yan-Li; Wei, Jun-Fen; Zhu, Bai-Ting; Tang, Jing-Xiang; Jiang, Yang-Yang; Meng, Jie; Yue, Ji-Rong; Lei, Peng] Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Pang, Ya-Yan; Li, Jun-Jie] Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Natl Clin Res Learning & Memory Disorders,Minist E, Chongqing 400014, Peoples R China"

通信作者："Yue, JR; Lei, P (通讯作者)，Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Dept Geriatr, Chengdu 610041, Sichuan, Peoples R China.; Yue, JR; Lei, P (通讯作者)，Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China."

来源：ZOOLOGICAL RESEARCH

ESI学科分类：PLANT & ANIMAL SCIENCE

WOS号：WOS:001043377400006

JCR分区：Q1

影响因子：4

年份：2023

卷号：44

期号：4

开始页：712

结束页：724

文献类型：Article

关键词：Delirium; Scopolamine; Cholinergic neuron; Neuronal activity; Brain network

摘要："Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice."

基金机构："National Natural Science Foundation of China [82071191, 82001129]; Natural Science Foundation of Sichuan Province [2022NSFSC1509]; National Clinical Research Center for Geriatrics of West China Hospital [Z2021LC001]; West China Hospital 1.3.5 Project for Disciplines of Excellence [ZYYC20009]"

基金资助正文："Foundation items: This work was supported by the National Natural Science Foundation of China (82071191, 82001129) , Natural Science Foundation of Sichuan Province (2022NSFSC1509) , National Clinical Research Center for Geriatrics of West China Hospital (Z2021LC001) , and West China Hospital 1.3.5 Project for Disciplines of Excellence (ZYYC20009)"