Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss
Qing Wang, 四川大学华西医院国家老年医学临床研究中心老年医学科, 生物治疗国家重点实验室, 四川 成都 610041, 中国, Xiang Zhang, Yu-Jie Guo, Ya‐Yan Pang, Junjie Li, Yanli Zhao, Jun-Fen Wei, Bai-Ting Zhu, Jing-Xiang Tang, Yangyang Jiang, Jie Meng, Jirong Yue, Lei Peng, 重庆医科大学儿童医院儿科研究所, 儿童发展与障碍教育部重点实验室, 国家儿童健康与障碍临床研究中心, 重庆市认知发展与学习记忆障碍转化医学研究重点实验室, 重庆400014, 中国
Abstract
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.