Aging effects on the dopamine transporter expression and compensatory mechanisms
Aging effects on the dopamine transporter expression and compensatory mechanisms
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DOI：
10.1016/j.neurobiolaging.2007.09.009
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发表时间：
2009-06-01
影响因子：
4.2
通讯作者：
Gonzalez-Hernandez, Tomas
中科院分区：
文献类型：
--
作者：
Cruz-Muros, Ignacio;Afonso-Oramas, Domingo;Gonzalez-Hernandez, Tomas
一些研究报道纹状体多巴胺（DA）摄取随着年龄的增长而下降，但潜在的机制尚不清楚。利用分子、生化和形态学技术，以及检测大鼠中纹状体系统中糖基化（80 kDa）和非糖基化（50 kDa）的DA转运体（DAT）形式的抗体，揭示了DAT在衰老过程中被翻译前和翻译后破坏。在中年（18个月），糖基化的DAT形式在纹状体末端的质膜中减少，而非糖基化形式在内质网-高尔基复体中积累。随后，老龄大鼠（24个月）的DAT合成也受到影响，DATmRNA和总DAT蛋白水平均下降。然而，老年大鼠体内（囊泡丰富的）胞室中DAT表达和磷酸化DAT片段的减少，以及其向终末质膜重新分布，纹状体突触体中膜DAT/总DAT比率增加的证据表明，da细胞激活了在正常衰老过程中维持DAT功能的代偿机制。(C) 2007爱思唯尔公司版权所有。
Several studies report that the striatal dopamine (DA) uptake declines with age, but the underlying mechanisms are still unclear. The use of molecular, biochemical and morphological techniques, and antibodies which detect the glycosylated (80 kDa) and non-glycosylated (50 kDa) DA transporter (DAT) forms in the rat mesostriatal system, reveals that DAT is pre- and post-translationally damaged during aging. In middle age (18 months), the glycosylated DAT form decreases in the plasma membrane of striatal terminals, and the non-glycosylated form is accumulated in the endoplasmic reticulum-Golgi complex. Thereafter, in aged rats (24 months), DAT synthesis is also affected as the decrease in both DATmRNA and total DAT protein levels suggests. However, the evidence of a decrease in both DAT expression in the endosomal (vesicle-enriched) compartment and the phosphorylated DAT fraction from middle age, as well as its compartmental redistribution towards the terminal plasma membrane, with an increase in the membrane DAT/total DAT ratio in striatal synapotosomes, in aged rats, indicate that DA-cells activate compensatory mechanisms directed at maintaining DAT function during normal aging. (C) 2007 Elsevier Inc. All rights reserved.