3-[3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine oxalate,a novel xanomeline derivative,improves neural cells proliferation and survival in adult mice

作     者：Xiaoliang Zhang Qiang Gong Shuang Zhang Lin Wang Yinghe Hu Haiming Shen Suzhen Dong 

作者机构：Key Laboratory of Brain Functional Genomics Ministry of Education East China Normal University Shanghai 200062 China Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development Institute for Advanced Interdisciplinary Research East China Normal University Shanghai 200062 China Institute of Aviation Medicine Civil Aviation University of China Tianjin 300300 China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2012年第7卷第1期

页      面：24-30页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 08[工学] 0905[农学-畜牧学] 09[农学] 090501[农学-动物遗传育种与繁殖] 

基　　金：supported by the National Natural Science Foundation of China, No. 31000574 the Fundamental Research Fund for the Central Universities, No.78210042 

主　　题：EUK1001 brain-derived neurotrophic factor MjM4 receptor neural regeneration proliferation survival 

摘      要：The present study analyzed the influence of 3-[3-（3-florophenyl-2-propyn-l-ylthio）-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-l-methylpyridine oxalate （EUK1001）, a novel xanomeline derivative of the M1/M4 receptor agonist, on hippocampal neurogenesis in adult C57BL6 mice. Results showed that 15-day EUK1001 treatment via intraperitoneal injection promoted neural cell proliferation in the dentate gyrus, although cell differentiation did not change. The majority of bromodeoxyuridine-positive cells co-expressed the immature neuronal marker doublecortin. In addition, the level of neurogenesis in the subventricular zone was not altered. Brain-derived neurotrophic factor mRNA expression was up-regulated following EUK1001 treatment, but no change was observed in expression of camp-responsive element binding protein 1, paired box gene 6, vascular endothelial growth factor alpha, neurogenic differentiation factor 1, and wingless-related mouse mammary tumor virus integration site 3A mRNA. These experimental findings indicated that EUK1001 enhanced proliferation and survival of hippocampal cells, possibly by increasing brain-derived neurotrophic factor expression.