首页|Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss
Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss
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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.
Department of Geriatrics and State Key Laboratory of Biotherapy,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China
Pediatric Research Institute,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Sichuan ProvinceNational Clinical Research Center for Geriatrics of West China HospitalWest China Hospital 1.3.5 Project for Disciplines of Excellence
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