Ceramide is involved in alcohol-induced neural proliferation  

作　　者：Zhixin Wang Tongxing Deng Jiexin Deng Jinbo Deng Xiaoqun Gao Yuanyuan Shi Bin Liu Zhanyou Ma Haixiao Jin 

机构地区：[1]Institute of Neurobiology,Henan University [2]Department of Anatomy,Basic Medical College,Zhengzhou University [3]Department of Anatomy,Luohe Medical College

出　　处：《Neural Regeneration Research》2013年第23期2178-2189,共12页中国神经再生研究（英文版）

基　　金：supported by the Technological Project of Science and Technology Department of Henan Province in China,No.122102310205;the National Natural Science Foundation of China,No.30771140,31070952,U1204311

摘　　要：Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C e increased in two genotypes of pups after ethanol exposure. Compared with witd-type pups, the expression level of the important activator protein of the ceramide/ceramide-l-phosphate pathway, protein kinase C a, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased ex- pression of protein kinase C a activating the ceramide/ceramide-l-phosphate pathway.Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C e increased in two genotypes of pups after ethanol exposure. Compared with witd-type pups, the expression level of the important activator protein of the ceramide/ceramide-l-phosphate pathway, protein kinase C a, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased ex- pression of protein kinase C a activating the ceramide/ceramide-l-phosphate pathway.

关 键 词：neural regeneration brain injury CERAMIDE neural cells PROLIFERATION prenatal alcohol exposure sphingomyelin synthase 2 knockout mice SPHINGOMYELIN sphingomyelin synthase cera-mide-l-phosphate fetal alcohol syndrome grants-supported paper NEUROREGENERATION 

分 类 号：R714.2[医药卫生—妇产科学]