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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo.
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Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo.

机译：纹状体胶质细胞源性神经营养因子在体内调节黑质多巴胺能神经元中自然细胞死亡。

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摘要

Dopamine (DA) neurons of the substantia nigra undergo a developmental cell death event that is biphasic, with peaks just after birth and at postnatal day 14. As envisioned by neurotrophic theory, this cell death is likely to be regulated by target interactions because it is augmented by their disruption. However, the nature of the trophic molecules mediating this regulation are unknown. We showed in vitro that glial cell line-derived neurotrophic factor (GDNF) is able to suppress apoptotic death in DA neurons in postnatal primary culture. We now demonstrate in vivo that administration of GDNF into the striatal target is able to suppress apoptosis. Consistent with a possible physiologic role for endogenous striatal GDNF in regulating this event, two anti-GDNF neutralizing antibodies augment cell death. These antibodies augment cell death only during the first (immediately postnatal) phase of the biphasic death event. We conclude that GDNF is the leading candidate for a target-derived neurotrophic factorfor the regulation of the early phase of natural cell death in DA neurons.
机译：黑质的多巴胺（DA）神经元经历双相发育性细胞死亡事件，在出生后和出生后第14天达到峰值。如神经营养学理论所设想的，该细胞死亡很可能受靶标相互作用的调节，因为它是因其破坏而增强。但是，调节这种调节的营养分子的性质是未知的。我们在体外显示，胶质细胞系衍生的神经营养因子（GDNF）能够抑制出生后原代培养中DA神经元的凋亡死亡。现在我们在体内证明了将GDNF施用到纹状体靶标中能够抑制细胞凋亡。与内源性纹状体GDNF在调节此事件中可能的生理作用相一致，两种抗GDNF中和抗体可增加细胞死亡。这些抗体仅在双相死亡事件的第一个阶段（出生后）才增加细胞死亡。我们得出的结论是，GDNF是靶源性神经营养因子的主要候选者，用于调节DA神经元中自然细胞死亡的早期。

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