Department of Chemistry and R. N. Adams Institute for Bioanalytical Chemistry, The University of Kansas, Lawrence, Kansas 66047-7572, USA.
J Neurochem. 2010 Feb;112(3):755-61. doi: 10.1111/j.1471-4159.2009.06501.x. Epub 2009 Nov 19.
Huntington's disease (HD) is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine (DA) in striatal brain slices from HD model R6/2 mice. When applying stimulus trains of 120 pulses, evoked DA release in wild-type (WT) slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool DA levels, amphetamine-induced DA efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-p-tyrosine. Slices from 12-week-old R6/2 mice released less DA than slices from WT mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool DA, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared with WT slices even though peak DA release was the same. Moreover, the number of DA reserve pool vesicles in R6/2 mice was less than half of that in WT. Therefore, our data suggest that the same number of DA molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer DA reserve pool vesicles available for mobilization.
亨廷顿病（HD）是一种致命的神经退行性运动障碍，其特征是纹状体优先且广泛退化。在这里，我们使用快速扫描循环伏安法研究 HD 模型 R6/2 小鼠纹状体脑片中储备池多巴胺（DA）的动员和外排。当应用 120 个脉冲的刺激序列时，在较高频率（50 和 60 Hz）下，WT 切片中的诱发出的 DA 释放大于 R6/2 切片中的释放。为了定量细胞溶质和储备池 DA 水平，在用四苯嗪或α-甲基-对酪氨酸预处理后测量安非他命诱导的 DA 外排。与 WT 小鼠相比，来自 12 周龄 R6/2 小鼠的切片释放出较少的 DA，而来自 6 周龄小鼠的切片则没有差异。用可卡因处理后，储备池 DA 的囊泡释放持续时间在 R6/2 切片中比 WT 切片更短，尽管 DA 释放的峰值相同。此外，R6/2 小鼠中的 DA 储备池囊泡数量不到 WT 小鼠的一半。因此，我们的数据表明，在 WT 和 R6/2 小鼠中，每个储备池囊泡中存在相同数量的 DA 分子，并且这些囊泡在两种基因型中都容易动员；然而，R6/2 小鼠中可用于动员的 DA 储备池囊泡数量较少。
