PROMOTION OF CENTRAL CHOLINERGIC AND DOPAMINERGIC NEURON DIFFERENTIATION BY BRAIN-DERIVED NEUROTROPHIC FACTOR BUT NOT NEUROTROPHIN 3

PROMOTION OF CENTRAL CHOLINERGIC AND DOPAMINERGIC NEURON DIFFERENTIATION BY BRAIN-DERIVED NEUROTROPHIC FACTOR BUT NOT NEUROTROPHIN 3
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DOI:
10.1073/pnas.88.3.961
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发表时间:
1991-02-01
影响因子:
11.1
通讯作者:
HEFTI, F
HEFTI, F
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KNUSEL, B;WINSLOW, JW;HEFTI, F

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重组人脑源性神经营养因子(rhBDNF)和神经营养因子3(rhNT-3)是新近克隆的两个与神经生长因子(NGF)密切相关的分子。 重组蛋白在含有基底前脑胆碱能神经元的分离的胎鼠脑细胞培养物中进行测试。 rhBDNF刺激胆碱能神经元的分化,类似于NGF,其被公认为这些细胞的神经营养因子。 然而,rhBDNF是特别有效的,在最初几天在体外,而rhNGF的刺激作用更明显的是在后来的发展的文化。 这一发现表明,存在不同的时间周期的胆碱能神经元的反应BDNF和NGF。 为了评估rhBDNF对胆碱能神经元作用的选择性,在含有多巴胺能细胞的腹侧中脑培养物中测试其作用。 与不影响中枢多巴胺能神经元的NGF相反,rhBDNF增加多巴胺摄取活性。 研究结果表明,BDNF刺激除了胆碱能神经元以外的其他细胞的存活或分化。
Recombinant human brain-derived neurotrophic factor (rhBDNF) and neurotrophin 3 (rhNT-3), two recently cloned molecules closely related to nerve growth factor (NGF), were produced from human cDNA expressed in human embryonic kidney cells. The recombinant proteins were tested in cultures of dissociated fetal rat brain cells containing basal forebrain cholinergic neurons. rhBDNF stimulated the differentiation of the cholinergic neurons, similar to NGF, which is well established as a neurotrophic factor for these cells. However, rhBDNF was particularly effective during the first few days in vitro, whereas the stimulatory action of rhNGF was more pronounced later in the development of the cultures. This finding indicates the existence of different time periods of responsiveness of the cholinergic neurons to BDNF and NGF. To assess the selectivity of the effect of rhBDNF on cholinergic neurons, its actions were tested in cultures of ventral mesencephalon containing dopaminergic cells. In contrast to NGF, which does not affect central dopaminergic neurons, rhBDNF increased dopamine uptake activity. The findings suggest that BDNF stimulates survival or differentiation of other cells besides the cholinergic neurons.