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亨廷顿病大鼠模型中兴奋性毒性作用后神经生长因子、脑源性神经营养因子和神经营养素-3表达的差异调节

Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 after excitotoxicity in a rat model of Huntington's disease.

作者信息

Canals J M, Marco S, Checa N, Michels A, Pérez-Navarro E, Arenas E, Alberch J

机构信息

Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Spain.

出版信息

Neurobiol Dis. 1998 Nov;5(5):357-64. doi: 10.1006/nbdi.1998.0211.

Abstract

In the present study we have evaluated changes in nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3 (NT-3) mRNA expression induced by different glutamate receptor agonists injected into the neostriatum. Up-regulation of NGF expression was observed at 24 h after intrastriatal quinolinate injection, an N-methyl-D-aspartate receptor agonist, and this increase was maintained up to 7 days after lesion. NGF up-regulation was also apparent in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) treatment from 6 to 16 h postinjection. Instead, BDNF was up-regulated only at 6 h after kainate or AMPA excitotoxicity. Interestingly, NT-3 mRNA was down-regulated from 10 to 16 h following AMPA lesion, while 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid injection enhanced NT-3 mRNA levels at 10 h. Our results show a specific neurotrophin response induced by stimulation of each glutamate receptor. These activity-dependent changes might be involved in neuronal plasticity processes and may underlie the differential vulnerability of striatal neurons observed in neurodegenerative disorders.

摘要

在本研究中,我们评估了向新纹状体注射不同谷氨酸受体激动剂后,神经生长因子(NGF)、脑源性神经营养因子和神经营养素3(NT-3)mRNA表达的变化。在注射N-甲基-D-天冬氨酸受体激动剂喹啉酸后24小时,观察到NGF表达上调,并且这种增加在损伤后持续7天。在注射α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)后6至16小时,NGF上调也很明显。相反,BDNF仅在海藻酸或AMPA兴奋性毒性作用后6小时上调。有趣的是,在AMPA损伤后10至16小时,NT-3 mRNA下调,而注射1S,3R-1-氨基环戊烷-1,3-二羧酸在10小时时增强了NT-3 mRNA水平。我们的结果显示了每种谷氨酸受体刺激诱导的特定神经营养因子反应。这些活动依赖性变化可能参与神经元可塑性过程,并可能是神经退行性疾病中观察到的纹状体神经元不同易损性的基础。

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