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 

机构地区：[1]Key Laboratory of Brain Functional Genomics, Ministry of Education, East China Normal University, Shanghai 200062, China [2]Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Institute for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China [3]Institute of Aviation Medicine, Civil Aviation University of China, Tianjin 300300, China

出　　处：《Neural Regeneration Research》2012年第1期24-30,共7页中国神经再生研究（英文版）

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

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.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.

关 键 词：EUK1001 brain-derived neurotrophic factor MjM4 receptor neural regeneration PROLIFERATION SURVIVAL 

分 类 号：Q424[生物学—神经生物学] Q492.4[生物学—生理学]