Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP.
Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP.
复制标题
易受 MPTP 影响的中脑神经元中多巴胺转运蛋白 mRNA 水平较高。
DOI：
10.1097/00001756-199710200-00027
复制
发表时间：
1997
期刊：
影响因子：
1.7
通讯作者：
German,DC
中科院分区：
文献类型：
--
作者：
Sanghera,MK;Manaye,K;McMahon,A;Sonsalla,PK;German,DC
神经毒素 MPTP 仅杀死某些中脑多巴胺能 (DA) 神经元，以产生帕金森病模型。多巴胺转运蛋白 (DAT) 对 MPTP 毒性很重要，因为要具有神经毒性，MPTP 代谢物必须首先通过 DAT 进入 DA 神经元。此外，MPTP 对含有假定的神经保护性钙结合蛋白 calbindin-D 28k (CB) 的 DA 神经元的毒性较小。本研究探讨了 DAT 活性和 CB 对于 C57BL/6 小鼠细胞对 MPTP 诱导的退化的脆弱性的相对重要性。研究发现，易受 MPTP 影响的细胞含有高水平的 DAT mRNA，而不易受 MPTP 影响的细胞则含有低水平的 DAT mRNA。此外，在有毒剂量的 MPTP 后剩余的少数黑质细胞仅含有低水平的 DAT mRNA。然而，细胞对 MPTP 毒性的抵抗力与含有 CB 的细胞之间没有很强的关系。这些数据为中脑细胞对 MPTP 毒性的脆弱性与 DAT 活性之间的直接相关性提供了体内证据。
THE neurotoxin MPTP kills only certain midbrain dopaminergic (DA) neurons to produce a model of Parkinson's disease. The dopamine transporter (DAT) is important to MPTP toxicity because to be neurotoxic, an MPTP metabolite must first gain access to the DA neuron via the DAT. Also, MPTP is less toxic to DA neurons that contain the putative neuroprotective calcium-binding protein calbindin-D 28k (CB). The present study examined the relative importance of DAT activity and CB for cellular vulnerability to MPTP-induced degeneration in the C57BL/6 mouse. Cells that were vulnerable to MPTP were found to contain high levels of DAT mRNA, whereas cells that were not vulnerable contained low levels. Also, the few substantia nigra cells remaining after a toxic dose of MPTP contained only low levels of DAT mRNA. However, there was not a strong relationship between cellular resistance to MPTP toxicity and cells containing CB. These data provide in vivo evidence for a direct correlation between midbrain cellular vulnerability to MPTP toxicity and the activity of the DAT.