Boron-Doped Diamond Microelectrodes Reveal Reduced Serotonin Uptake Rates in Lymphocytes from Adult Rhesus Monkeys Carrying the Short Allele of the 5-HTTLPR.
Boron-Doped Diamond Microelectrodes Reveal Reduced Serotonin Uptake Rates in Lymphocytes from Adult Rhesus Monkeys Carrying the Short Allele of the 5-HTTLPR.
复制标题
掺硼金刚石微电极显示，携带 5-HTTLPR 短等位基因的成年恒河猴的淋巴细胞中血清素摄取率降低。
DOI：
10.1021/cn900012y
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发表时间：
2010-01-20
影响因子：
5
通讯作者：
Andrews, Anne M.
中科院分区：
文献类型：
--
作者：
Singh, Yogesh S.;Sawarynski, Lauren E.;Michael, Heather M.;Ferrell, Robert E.;Murphey-Corb, Michael A.;Swain, Greg M.;Patel, Bhavik A.;Andrews, Anne M.
关键词：
通过高速计时电流分析法逐秒解析的摄取揭示了与遗传变异相关的大脑血清素转运蛋白功能的重要差异。在这里，我们使用计时安培法来研究与恒河猴血清素转运蛋白基因连锁多态性（rh5-HTTLPR）相关的原代淋巴细胞中血清素转运的变化，这是一种启动子多态性，其直系同源物仅出现在包括人类在内的高级灵长类动物中。淋巴细胞的血清素清除依赖于 Na+，并受到血清素选择性再摄取抑制剂帕罗西汀 (Paxil®) 的抑制，表明血清素转运蛋白的主动摄取。此外，带有一个或两个 rh5-HTTLPR 短“s”等位基因拷贝 (s/s<s/l<l/l) 的猴子的淋巴细胞中，血清素摄取率明显降低。这些发现表明，在成年期，天然表达血清素转运蛋白的外周血细胞中存在与 rh5-HTTLPR 相关的血清素摄取变化。此外，他们建议淋巴细胞可以用作外周生物标志物，用于研究血清素转运蛋白功能的遗传或药理学改变。与之前在大脑中使用的碳纤维微电极相比，使用掺硼金刚石微电极来测量血清素的吸收，使得这些高灵敏度和高分辨率的测量成为可能。硼掺杂金刚石微电极显示出优异的信噪比和信背景比，这主要是由于低背景电流，并且在暴露于淋巴细胞或高浓度血清素时具有高度抗污染性。
Uptake resolved by high-speed chronoamperometry on a second-by-second basis has revealed important differences in brain serotonin transporter function associated with genetic variability. Here, we use chronoamperometry to investigate variations in serotonin transport in primary lymphocytes associated with the rhesus serotonin transporter gene-linked polymorphism (rh5-HTTLPR), a promoter polymorphism whose orthologs occur only in higher order primates including humans. Serotonin clearance by lymphocytes is Na+-dependent and inhibited by the serotonin-selective reuptake inhibitor paroxetine (Paxil®), indicative of active uptake by serotonin transporters. Moreover, reductions in serotonin uptake rates are evident in lymphocytes from monkeys with one or two copies of the short ‘s’ allele of the rh5-HTTLPR (s/s<s/l<l/l). These findings illustrate that rh5-HTTLPR-related alterations in serotonin uptake are present during adulthood in peripheral blood cells natively expressing serotonin transporters. Moreover, they suggest that lymphocytes can be used as peripheral biomarkers for investigating genetic or pharmacologic alterations in serotonin transporter function. Use of boron-doped diamond microelectrodes for measuring serotonin uptake, in contrast to carbon fiber microelectrodes used previously in the brain, enabled these high-sensitivity and high-resolution measurements. Boron-doped diamond microelectrodes show excellent signal-to-noise and signal-to-background ratios due mainly to low background currents and are highly resistant to fouling when exposed to lymphocytes or high concentrations of serotonin.
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DOI：
10.1097/01.alc.0000067976.62827.ed
发表时间：
2003-05-01
影响因子：
3.2
作者：
Barr, CS;Newman, TK;Higley, JD
通讯作者：
Higley, JD
影响因子：
7.4
作者：
Granger, MC;Witek, M;Swain, GM
通讯作者：
Swain, GM
影响因子：
2.2
作者：
Andersen, SL;Dumont, NL;Teicher, MH
通讯作者：
Teicher, MH
影响因子：
5.3
作者：
Gelernter, J;Kranzler, H;Cubells, JF
通讯作者：
Cubells, JF
影响因子：
3.6
作者：
Bengel, D;Murphy, DL;Lesch, KP
通讯作者：
Lesch, KP