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Brain-derived neurotrophic factor protects neurons from GdCl_3-induced impairment in neuron-astrocyte co-cultures

Brain-derived neurotrophic factor protects neurons from GdCl_3-induced impairment in neuron-astrocyte co-cultures

作     者:XIA Qing, FENG XuDong, YUAN Lan, WANG Kui & YANG XiaoDa State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 

作者机构:1. State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology School of Pharmaceutical Sciences Peking University Beijing 100191 China 

出 版 物:《Science China Chemistry》 (中国科学(化学英文版))

年 卷 期:2010年第53卷第10期

页      面:2193-2199页

核心收录:

学科分类:1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基  金:funded by the National Natural Science Foundation of China (20901005 and 20637010) the Research Fund for the Doctoral Program of Higher Education (200800011056) 

主  题:gadolinium brain-derived neurotrophic factor BDNF co-culture astrocytes neurons 

摘      要:Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl3 have been investigated in both neuron monoculture and astrocyte-neuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl3-induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl3-induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd3+-induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understand- ing the neurotoxic actions of gadolinium probes .

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