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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RETROGRADE AXONAL TRANSPORT OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR IN THE ADULT NIGROSTRIATAL SYSTEM SUGGESTS A TROPHIC ROLE IN THE ADULT
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RETROGRADE AXONAL TRANSPORT OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR IN THE ADULT NIGROSTRIATAL SYSTEM SUGGESTS A TROPHIC ROLE IN THE ADULT

机译：胶质细胞源性神经营养因子在成人神经系统中的逆行轴突转运提示该营养作用在成人中

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摘要

The recently cloned, distant member of the transforming growth factor beta (TGF-beta) family, glial cell line-derived neurotrophic factor (GDNF), has potent trophic actions on fetal mesencephalic dopamine neurons, GDNF also has protective and restorative activity on adult mesencephalic dopaminergic neurons and potently protects motoneurons from axotomy-induced cell death. However, evidence for a role for endogenous GDNF as a target-derived trophic factor in adult midbrain dopaminergic circuits requires documentation of specific transport from the sites of synthesis in the target areas to the nerve cell bodies themselves, Here, we demonstrate that GDNF is retrogradely transported by mesencephalic dopamine neurons of the nigrostriatal pathway, The pattern of retrograde transport following intrastriatal injections indicates that there may be subpopulations of neurons that are GDNF responsive, Retrograde axonal transport of biologically active I-125-labeled GDNF was inhibited by an excess of unlabeled GDNF but not by an excess of cytochrome c. Specificity was further documented by demonstrating that another TGF-beta family member, TGF-beta 1, did not appear to affect retrograde transport, Retrograde transport was also demonstrated by immunohistochemistry by using intrastriatal injections of unlabeled GDNF, GDNF immunoreactivity was found specifically in dopamine nerve cell bodies of the substantia nigra pars compacta distributed in granules in the soma and proximal dendrites, Our data implicate a specific receptor-mediated uptake mechanism operating in the adult. Taken together, the present findings suggest that GDNF acts endogenously as a target-derived physiological survival/maintenance factor for dopaminergic neurons. [References: 31]
机译：胶质细胞源性神经营养因子（GDNF）是最近被克隆的，转化生长因子β（TGF-beta）家族的远距离成员，对胎儿中脑多巴胺神经元具有有效的营养作用，GDNF对成人中脑也具有保护和修复作用多巴胺能神经元并有效保护运动神经元免受轴突切开术诱导的细胞死亡。但是，内源性GDNF在成人中脑多巴胺能回路中作为靶源营养因子起作用的证据需要从目标部位的合成位点到神经细胞体本身的特异性转运的证明，在这里，我们证明GDNF是逆行的通过纹状体内途径的中脑多巴胺神经元转运，纹状体内注射后逆行转运的模式表明，可能存在对GDNF有反应的神经元亚群，生物活性I-125标记的GDNF的轴突逆行转运受到过量未标记的抑制GDNF，但不过量的细胞色素c。通过证明另一种TGF-beta家族成员TGF-beta 1似乎不影响逆行转运，进一步证明了特异性。通过组织内注射未标记的GDNF的免疫组织化学也证实了逆行转运，特别是在多巴胺神经中发现了GDNF免疫反应性黑质致密部的致密细胞体分布在躯体和近端树突的颗粒中。我们的数据暗示了在成年人中起作用的特定受体介导的摄取机制。综上所述，本发明结果提示GDNF内源性地充当多巴胺能神经元的靶标衍生的生理存活/维持因子。 [参考：31]

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