Neural Regeneration Research ›› 2012, Vol. 7 ›› Issue (1): 24-30.

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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

Xiaoliang Zhang1, Qiang Gong2, Shuang Zhang2, Lin Wang2, Yinghe Hu1, 2, Haiming Shen3, Suzhen Dong1, 2   

  1. 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
  • Received:2011-09-19 Revised:2011-11-22 Online:2012-01-05 Published:2012-01-05
  • Contact: Suz-hen Dong, Ph.D., Research assistant, Key Laboratory of Brain Functional Genomics, Ministry of Education, East China Normal University, Shanghai 200062, China; Shanghai Engineering Re-search Center of Molecular Therapeutics and New Drug Development, Institute for Advanced Interdisciplinary Research, East China Nor-mal University, Shanghai 200062, China szdong@brain.ecnu.edu.cn
  • About author:Xiaoliang Zhang, Key Labor-atory of Brain Functional Genomics, Ministry of Edu-cation, East China Normal University, Shanghai 200062, China

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Abstract:

The present study analyzed the influence of 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1-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.

Key words: EUK1001, brain-derived neurotrophic factor, M1/M4 receptor, neural regeneration, proliferation, survival