致密部
黑质
被盖腹侧区
多巴胺能
多巴胺
神经科学
生物
被盖
神经退行性变
帕金森病
中脑
内科学
中枢神经系统
医学
疾病
作者
Xóchitl Flores-Ponce,Iván Velasco
出处
期刊:Metabolomics
[Springer Nature]
日期:2024-10-13
卷期号:20 (6)
标识
DOI:10.1007/s11306-024-02181-4
摘要
Abstract Background Dopaminergic neurons from the substantia nigra pars compacta (SNc) have a higher susceptibility to aging-related degeneration, compared to midbrain dopaminergic cells present in the ventral tegmental area (VTA); the death of dopamine neurons in the SNc results in Parkinson´s disease (PD). In addition to increased loss by aging, dopaminergic neurons from the SNc are more prone to cell death when exposed to genetic or environmental factors, that either interfere with mitochondrial function, or cause an increase of oxidative stress. The oxidation of dopamine is a contributing source of reactive oxygen species (ROS), but this production is not enough to explain the differences in susceptibility to degeneration between SNc and VTA neurons. Aim of review In this review we aim to highlight the intrinsic differences between SNc and VTA dopamine neurons, in terms of gene expression, calcium oscillations, bioenergetics, and ROS responses. Also, to describe the changes in the pentose phosphate pathway and the induction of apoptosis in SNc neurons during aging, as related to the development of PD. Key scientific concepts of review Recent work showed that neurons from the SNc possess intrinsic characteristics that result in metabolic differences, related to their intricate morphology, that render them more susceptible to degeneration. In particular, these neurons have an elevated basal energy metabolism, that is required to fulfill the demands of the constant firing of action potentials, but at the same time, is associated to higher ROS production, compared to VTA cells. Finally, we discuss how mutations related to PD affect metabolic pathways, and the related mechanisms, as revealed by metabolomics.
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