Perez de la Mora Miguel, Hernandez-Mondragon Carlos, Crespo-Ramirez Minerva, Rejon-Orantes José, Borroto-Escuela Dasiel O, Fuxe Kjell
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Neuroscience. 2020 Jul 15;439:301-318. doi: 10.1016/j.neuroscience.2019.07.026. Epub 2019 Jul 23.
The dopaminergic system integrated by cell groups distributed in several brain regions exerts a modulatory role in brain. Particularly important for this task are the mesencephalic dopamine neurons, which from the substantia nigra and ventral tegmental area project to the dorsal striatum and the cortical/subcortical limbic systems, respectively. Dopamine released from these neurons operates mainly via the short distance extrasynaptic volume transmission and activates five different dopaminergic receptor subtypes modulating synaptic GABA and glutamate transmission. To accomplish this task dopaminergic neurons keep mutual modulating interactions with neurons of other neurotransmitter systems, including allosteric receptor-receptor interactions in heteroreceptor complexes. As a result of its modulatory role dopaminergic mechanisms are involved in either the etiology or physiopathology of many brain diseases such as Parkinsońs disease and schizophrenia. The aim of this work is to review some novel and conventional approaches that either have been used or are currently employed to treat these diseases. Particular attention is paid to the approaches derived from the knowledge recently acquired in the realm of receptor-receptor interactions taking place through multiple dopamine heteroreceptor complexes in the plasma membrane. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
由分布在多个脑区的细胞群整合而成的多巴胺能系统在大脑中发挥调节作用。对于这项任务而言，特别重要的是中脑多巴胺神经元，它们分别从黑质和腹侧被盖区投射到背侧纹状体以及皮质/皮质下边缘系统。这些神经元释放的多巴胺主要通过短距离的突触外容积传递起作用，并激活五种不同的多巴胺能受体亚型，从而调节突触GABA和谷氨酸传递。为了完成这项任务，多巴胺能神经元与其他神经递质系统的神经元保持相互调节的相互作用，包括异源受体复合物中的变构受体 - 受体相互作用。由于其调节作用，多巴胺能机制参与了许多脑部疾病如帕金森病和精神分裂症的病因学或病理生理学过程。这项工作的目的是综述一些已被使用或目前正在用于治疗这些疾病的新颖和传统方法。特别关注的是源自最近在质膜中通过多种多巴胺异源受体复合物发生的受体 - 受体相互作用领域所获得知识的方法。本文是名为：纪念里卡多·米莱迪——二十世纪至二十一世纪杰出神经科学家的特刊的一部分。
