Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
Departments of Psychiatry, Neurology, and Pharmacology, Columbia University Medical Center, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
Cell Chem Biol. 2021 Jun 17;28(6):748-764. doi: 10.1016/j.chembiol.2021.04.005. Epub 2021 Apr 23.
Dopamine is a modulatory neurotransmitter involved in learning, motor functions, and reward. Many neuropsychiatric disorders, including Parkinson's disease, autism, and schizophrenia, are associated with imbalances or dysfunction in the dopaminergic system. Yet, our understanding of these pervasive public health issues is limited by our ability to effectively image dopamine in humans, which has long been a goal for chemists and neuroscientists. The last two decades have witnessed the development of many molecules used to trace dopamine. We review the small molecules, nanoparticles, and protein sensors used with fluorescent microscopy/photometry, MRI, and PET that shape dopamine research today. None of these tools observe dopamine itself, but instead harness the biology of the dopamine system-its synthetic and metabolic pathways, synaptic vesicle cycle, and receptors-in elegant ways. Their advantages and weaknesses are covered here, along with recent examples and the chemistry and biology that allow them to function.
多巴胺是一种参与学习、运动功能和奖励的调制神经递质。许多神经精神疾病,包括帕金森病、自闭症和精神分裂症,都与多巴胺能系统的失衡或功能障碍有关。然而,我们对这些普遍存在的公共卫生问题的理解受到我们在人类中有效成像多巴胺的能力的限制,这一直是化学家们和神经科学家们的目标。在过去的二十年中,已经开发出许多用于追踪多巴胺的分子。我们回顾了用于荧光显微镜/光度法、MRI 和 PET 的小分子、纳米颗粒和蛋白质传感器,这些方法塑造了当今的多巴胺研究。这些工具都没有直接观察到多巴胺本身,而是以巧妙的方式利用多巴胺系统的生物学特性,包括其合成和代谢途径、突触小泡循环和受体。这里涵盖了它们的优缺点,以及最近的例子和使它们发挥作用的化学和生物学。