Voltammetric and mathematical evidence for dual transport mediation of serotonin clearance in vivo.
Voltammetric and mathematical evidence for dual transport mediation of serotonin clearance in vivo.
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DOI：
10.1111/jnc.12733
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发表时间：
2014-08
影响因子：
4.7
通讯作者：
Hashemi P
中科院分区：
文献类型：
--
作者：
Wood KM;Zeqja A;Nijhout HF;Reed MC;Best J;Hashemi P
神经递质血清素是大脑许多功能的基础。了解血清素神经化学对于改善神经精神疾病（如抑郁症）的治疗非常重要。抗抑郁药通常通过5-羟色胺转运蛋白（SERT）靶向5-羟色胺清除，并具有可变的临床效果。针对包括血清素自身受体在内的其他系统的辅助疗法在临床上也各不相同，并带来不良后果。快速扫描循环伏安法（FSCV）通过提供体内5-羟色胺动力学的实时化学信息，特别适合于研究对5-羟色胺清除率和自身受体的抗抑郁作用。然而，体内5-羟色胺反应的复杂性质使得难以用已建立的动力学模型解释实验数据。在这里，我们电刺激小鼠内侧前脑束（MFB）挑起和检测终端5-羟色胺在黑质网状（SNr）。在响应MFB刺激，我们发现三个动态不同的血清素信号。为了解释这些信号，我们开发了一个计算模型，该模型支持两种独立的5-羟色胺再摄取机制（高亲和力、低效率再摄取机制和低亲和力、高效率再摄取系统），并支持5-羟色胺自身受体的重要抑制作用。我们的数据和分析，提供了强大的伏安法和理论方法的结合，给大脑中的5-羟色胺动力学的化学异质性的新的理解。这种多样的多巴胺能基质可能有助于抗抑郁药的临床变异性。
The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants.
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影响因子：
5
作者：
Hashemi, Parastoo;Walsh, Paul L.;Wightman, R. Mark
通讯作者：
Wightman, R. Mark
影响因子：
4.7
作者：
Daws, LC;Gould, GG;Frazer, S
通讯作者：
Frazer, S
影响因子：
4.7
作者：
Moquin, Keith F.;Michael, Adrian C.
通讯作者：
Michael, Adrian C.
DOI：
10.1073/pnas.1201547109
发表时间：
2012-07-17
影响因子：
11.1
作者：
Hashemi, Parastoo;Dankoski, Elyse C.;Wightman, R. Mark
通讯作者：
Wightman, R. Mark
影响因子：
3.6
作者：
Haenisch, Britta;Boenisch, Heinz
通讯作者：
Boenisch, Heinz