首页|期刊导航|中华医学杂志（英文版）|Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro
中华医学杂志（英文版）2011，Vol.124Issue(20)：3373-3377,5.DOI:10.3760/cma.j.issn.0366-6999.2011.20.030
Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro
Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro
摘要
Abstract
Background Wallerian degeneration is a self-destructive process of axonal degeneration that occurs after an axonal injury or during neurodegenerative disorders such as Parkinson's or Alzheimer's disease.Recent studies have found that the activity of the nicotinamide adenine dinucleotide (NAD) synthase enzyme,nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) can affect the rate of Wallerian degeneration in mice and drosophila.NMNAT1 protects neurons and axons from degeneration.However,the role of NMNAT1 in neurons of central nervous system is still not well understood.Methods We set up the culture of primary mouse neurons in vitro and manipulated the expression level of NMNAT1 by RNA interference and gene overexpression methods.Using electroporation transfection we can up-regulate or down-regulate NMNAT1 in cultured mouse dendrites and axons and study the neuronal morphogenesis by immunocytochemistry.In all functional assays,FK-866 (CAS 658084-64-1),a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase was used as a pharmacological and positive control.Results Our results showed that knocking down NMNAT1 by RNA interference led to a marked decrease in dendrite outgrowth and branching and a significant decrease in axon growth and branching in developing cortical neurons in vitro.Conclusions These findings reveal a novel role for NMNAT1 in the morphogenesis of developing cortical neurons,which indicate that the loss of function of NMNAT1 may contribute to different neurodegenerative disorders in central nervous system.关键词
nicotinamide-nucleotide/adenylyltransferase/neurogenesis/RNA interference/gene expressionKey words
nicotinamide-nucleotide/adenylyltransferase/neurogenesis/RNA interference/gene expression引用本文复制引用
ZHAO Hong,ZHANG Jing-yu,YANGZi-chao,LIU Ming,GANG Bao-zhi,ZHAO Qing-jie..Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro[J].中华医学杂志（英文版）,2011,124(20):3373-3377,5.基金项目
This work was supported by a grant from the Natural Science Foundation of Heilongjiang Province of China (2009). （2009）
