Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat:: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factor
Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat:: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factor
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DOI：
10.1046/j.1460-9568.2001.01356.x
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发表时间：
2001-01-01
影响因子：
3.4
通讯作者：
Björklund, A
中科院分区：
文献类型：
--
作者：
Vaudano, E;Rosenblad, C;Björklund, A
本研究的目的是确定是否诱导和磷酸化的转录因子c-Jun与病变诱导的黑质多巴胺能神经元的死亡，如果这种细胞反应是由神经胶质细胞系源性神经营养因子调制。在成年大鼠中，纹状体内注射B-羟基多巴胺诱导的多巴胺能神经元细胞死亡延迟，导致黑质背侧部c-Jun和磷酸化cJun免疫反应性核的数量显着增加。在可以检测到黑质神经元的任何显著损失之前（在损伤后第7天），反应是最大的，并且仅限于多巴胺能神经元。同样，6-羟基多巴胺损伤的纹状体多巴胺能神经末梢或兴奋性毒性损伤的纹状体靶神经元在新生大鼠导致c-Jun和磷酸化cJun免疫反应黑质细胞核的数量增加，黑质多巴胺能神经元的损失之前。相比之下，在成年大鼠纹状体靶神经元的兴奋性毒性损伤后，导致黑质多巴胺能神经元的萎缩而不是细胞死亡，在纹状体内6-羟基多巴胺损伤后第3天单次注射10 μ g胶质细胞系衍生的神经营养因子可减少c-Jun和磷酸化c-Jun的数量。免疫反应性核在黑质和保护多巴胺能神经元从随后的细胞死亡。我们得出结论，c-Jun诱导和磷酸化！可能参与导致体内黑质多巴胺能神经元死亡的细胞事件，并且这种反应可以由胶质细胞系衍生的神经营养因子调节。
This study was designed to determine whether induction and phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of dopaminergic neurons of the substantia nigra pars compacta, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor. In adult rats, delayed dopaminergic neuron cell death induced by intrastriatal B-hydroxydopamine injection led to a marked increase in the number of both c-Jun- and phosphorylated cJun-immunoreactive nuclei in the substantia nigra pars compacta. The response was maximal before any significant loss of nigral neurons could be detected (on day 7 post lesion) and was confined to the dopaminergic neurons. Similarly, 6-hydroxydopamine lesion of the striatal dopaminergic terminals or excitotoxic lesion of the striatal target neurons in neonatal rats resulted in an increased number of c-Jun- and phosphorylated cJun-immunoreactive nigral nuclei that preceded the loss of nigral dopaminergic neurons. By contrast, after an excitotoxic lesion of the striatal target neurons in the adult rat, resulting in atrophy but not cell death of the nigral dopaminergic neurons, no upregulation of either c-Jun or phosphorylated c-Jun was found. A single injection of 10 mug of glial-cell-line-derived-neurotrophic factor given at day 3 after the intrastriatal 6-hydroxydopamine lesion reduced the number of c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra and protected the dopaminergic neurons from the ensuing cell death. We conclude that c-Jun induction and phosphorylation! may be involved in the cellular events leading to death of nigral dopaminergic neurons in vivo and that this response can be modulated by glial-cell-line-derived-neurotrophic factor.