Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, Germany.
TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal, 14558 Nuthetal, Germany.
Molecules. 2023 Jul 13;28(14):5373. doi: 10.3390/molecules28145373.
Neurotransmitters like dopamine (DA), serotonin (SRT), γ-aminobutyric acid (GABA) and acetylcholine (ACh) are messenger molecules that play a pivotal role in transmitting excitation between neurons across chemical synapses, thus enabling complex processes in the central nervous system (CNS). Balance in neurotransmitter homeostasis is essential, and altered neurotransmitter levels are associated with various neurological disorders, e.g., loss of dopaminergic neurons (Parkinson's disease) or altered ACh synthesis (Alzheimer's disease). Therefore, it is crucial to possess adequate tools to assess precise neurotransmitter levels, and to apply targeted therapies. An established in vivo model to study neurotoxicity is the model organism (), as its neurons have been well characterized and functionally are analogous to mammals. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method including a sample preparation assuring neurotransmitter stability, which allows a simultaneous neurotransmitter quantification of DA, SRT, GABA and ACh in , but can easily be applied to other matrices. LC-MS/MS combined with isotope-labeled standards is the tool of choice, due to its otherwise unattainable sensitivity and specificity. Using together with our analytically validated and verified method provides a powerful tool to evaluate mechanisms of neurotoxicity, and furthermore to identify possible therapeutic approaches.
神经递质，如多巴胺（DA）、血清素（SRT）、γ-氨基丁酸（GABA）和乙酰胆碱（ACh），是在化学突触中在神经元之间传递兴奋的信使分子，从而使中枢神经系统（CNS）中的复杂过程成为可能。神经递质动态平衡至关重要，而神经递质水平的改变与各种神经疾病有关，例如多巴胺能神经元丧失（帕金森病）或 ACh 合成改变（阿尔茨海默病）。因此，拥有足够的工具来评估精确的神经递质水平并应用靶向治疗至关重要。研究神经毒性的成熟体内模型是模式生物（），因为其神经元已经得到很好的描述，并且在功能上与哺乳动物类似。我们开发了一种液相色谱-串联质谱（LC-MS/MS）方法，包括一种确保神经递质稳定性的样品制备，该方法允许同时定量 DA、SRT、GABA 和 ACh 在 中的含量，但很容易应用于其他基质。LC-MS/MS 与同位素标记标准品结合使用是首选工具，因为它具有其他方法无法达到的灵敏度和特异性。使用 结合我们经过分析验证的方法提供了一种强大的工具来评估神经毒性的机制，并进一步确定可能的治疗方法。
