Qi Guoyuan, Mi Yashi, Yin Fei
Center for Innovation in Brain Science, University of Arizona Health Sciences, Tucson, AZ, United States.
Department of Pharmacology, College of Medicine Tucson, Tucson, AZ, United States.
Front Physiol. 2020 Jan 8;10:1531. doi: 10.3389/fphys.2019.01531. eCollection 2019.
As an organ with a highly heterogenous cellular composition, the brain has a bioenergetic system that is more complex than peripheral tissues. Such complexities are not only due to the diverse bioenergetic phenotypes of a variety of cell types that differentially contribute to the metabolic profile of the brain, but also originate from the bidirectional metabolic communications and coupling across cell types. While brain energy metabolism and mitochondrial function have been extensively investigated in aging and age-associated neurodegenerative disorders, the role of various cell types and their inter-cellular communications in regulating brain metabolic and synaptic functions remains elusive. In this review, we summarize recent advances in differentiating bioenergetic phenotypes of neurons, astrocytes, and microglia in the context of their functional specificity, and their metabolic shifts upon aging and pathological conditions. Moreover, the metabolic coordination between the two most abundant cell populations in brain, neurons and astrocytes, is discussed regarding how they jointly establish a dynamic and responsive system to maintain brain bioenergetic homeostasis and to combat against threats such as oxidative stress, lipid toxicity, and neuroinflammation. Elucidating the mechanisms by which brain cells with distinctive bioenergetic phenotypes individually and collectively shape the bioenergetic system of the brain will provide rationale for spatiotemporally precise interventions to sustain a metabolic equilibrium that is resilient against synaptic dysfunction in aging and neurodegeneration.
作为一个细胞组成高度异质的器官，大脑具有比外周组织更为复杂的生物能量系统。这种复杂性不仅源于多种细胞类型具有不同的生物能量表型，它们对大脑代谢特征的贡献各不相同，还源于不同细胞类型之间双向的代谢通讯与耦合。虽然在衰老及与年龄相关的神经退行性疾病中，大脑能量代谢和线粒体功能已得到广泛研究，但各种细胞类型及其细胞间通讯在调节大脑代谢和突触功能中的作用仍不清楚。在这篇综述中，我们总结了在神经元、星形胶质细胞和小胶质细胞的功能特异性背景下，区分它们生物能量表型的最新进展，以及它们在衰老和病理条件下的代谢变化。此外，还讨论了大脑中数量最多的两类细胞——神经元和星形胶质细胞之间的代谢协调，即它们如何共同建立一个动态且反应灵敏的系统，以维持大脑生物能量稳态，并抵御氧化应激、脂质毒性和神经炎症等威胁。阐明具有独特生物能量表型的脑细胞如何单独及共同塑造大脑生物能量系统的机制，将为时空精确干预提供理论依据，以维持一种能够抵御衰老和神经退行性变中突触功能障碍的代谢平衡。
