Department of Pharmacology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
IdISNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
Int J Mol Sci. 2022 Mar 29;23(7):3785. doi: 10.3390/ijms23073785.
The brain is one of the most energy-consuming organs in the body. Satisfying such energy demand requires compartmentalized, cell-specific metabolic processes, known to be complementary and intimately coupled. Thus, the brain relies on thoroughly orchestrated energy-obtaining agents, processes and molecular features, such as the neurovascular unit, the astrocyte-neuron metabolic coupling, and the cellular distribution of energy substrate transporters. Importantly, early features of the aging process are determined by the progressive perturbation of certain processes responsible for adequate brain energy supply, resulting in brain hypometabolism. These age-related brain energy alterations are further worsened during the prodromal stages of neurodegenerative diseases, namely Alzheimer's disease (AD), preceding the onset of clinical symptoms, and are anatomically and functionally associated with the loss of cognitive abilities. Here, we focus on concrete neuroenergetic features such as the brain's fueling by glucose and lactate, the transporters and vascular system guaranteeing its supply, and the metabolic interactions between astrocytes and neurons, and on its neurodegenerative-related disruption. We sought to review the principles underlying the metabolic dimension of healthy and AD brains, and suggest that the integration of these concepts in the preventive, diagnostic and treatment strategies for AD is key to improving the precision of these interventions.
大脑是人体中最耗能的器官之一。满足这种能量需求需要分区的、细胞特异性的代谢过程,这些过程被认为是互补的且紧密耦联的。因此,大脑依赖于经过精心协调的能量获取剂、过程和分子特征,如神经血管单元、星形胶质细胞-神经元代谢偶联和能量底物转运体的细胞分布。重要的是,衰老过程的早期特征取决于负责大脑能量供应的某些过程的逐渐失调,导致脑代谢减少。在神经退行性疾病(如阿尔茨海默病)的前驱阶段,这些与年龄相关的大脑能量改变进一步恶化,即在出现临床症状之前,与认知能力丧失在解剖和功能上相关。在这里,我们专注于具体的神经能量特征,如大脑对葡萄糖和乳酸的供能、保证其供应的转运体和血管系统,以及星形胶质细胞和神经元之间的代谢相互作用,以及与神经退行性相关的破坏。我们试图综述健康大脑和 AD 大脑代谢维度的基本原则,并提出将这些概念整合到 AD 的预防、诊断和治疗策略中是提高这些干预措施精确性的关键。