专题2:脑中风与神经退行性疾病

Topic 2 Stroke and Neurodegenerative Diseases(T2-1~T2-82)

T2-1 N,N-dimethyltryptamine,a natural psychedelic,rap⁃idly improves spatial memory and hippocampal longterm potentiation:a potential rapid-acting therapy for dementia-associated wandering CHENG Dan1,LEI Zhuogui2,Benjamin Chun-Kit TONG3,Catherine Kin CHIU4,LI Ying2,King-Ho CHEUNG3,ZHANG Zhangjin1,5(1.School of Chinese Medicine,4.Department of Psycholo⁃gy,LKS Faculty of Medicine,the University of HongKong,HongKong,China;2.Department of Neuroscience,City Uni⁃versity of HongKong,HongKong,China;3.School of Chins⁃es Medicine and Mr.and Mrs.Ko Chi Ming Centre for Par⁃kinson’s Disease Research,HongKong Baptist University,HongKong,China;5.Department of Chinese Medicine,the University of Hong Kong-Shenzhen Hospital,Shenzhen 518000,China)Abstract:There is no fast-acting treatment strate⁃gies against Alzheimer′s disease(AD),in particular dementia-related wandering.N,N-dimethyltryptamine(DMT)is a natural psychedelic that may have rapid-onset nootropic effects.In this study,5×FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg·kg-1 DMT and tested at 0.5,1,and 2 h thereafter in Y-maze for spatial memory.5×FAD transgenic mice exhibited pro⁃nounced decreases in time spent,number entered,and distance travelled in the novel arm of Y-maze.DMT at 12 mg·kg-1 partially or completely reversed the three behavioral indices at multiple time points,up to 2 h post injection.The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT,showing approximately 30 min to reach the maximum concentra⁃tion in the brain tissue.The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP),an electrophysiological feature of memory forma⁃tion and consolidation.