Vardjan Nina, Verkhratsky Alexej, Zorec Robert
Laboratory of Cell Engineering, Celica BIOMEDICAL, 1000 Ljubljana, Slovenia.
Laboratory of Neuroendocrinology & Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2017 Feb 8;18(2):358. doi: 10.3390/ijms18020358.
Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced. How simultaneous energy procurement in a relatively extended area of the brain takes place is poorly understood. This mechanism is likely to be impaired in neurodegeneration, for example in Alzheimer's disease, the hallmark of which is brain hypometabolism. Astrocytes, the main neural cell type producing and storing glycogen, a form of energy in the brain, also hold the key to metabolic and homeostatic support in the central nervous system and are impaired in neurodegeneration, contributing to the slow decline of excitation-energy coupling in the brain. Many mechanisms are affected, including cell-to-cell signalling. An important question is how changes in cellular signalling, a process taking place in a rather short time domain, contribute to the neurodegeneration that develops over decades. In this review we focus initially on the slow dynamics of Alzheimer's disease, and on the activity of locus coeruleus, a brainstem nucleus involved in arousal. Subsequently, we overview much faster processes of vesicle traffic and cytosolic calcium dynamics, both of which shape the signalling landscape of astrocyte-neurone communication in health and neurodegeneration.
尽管中枢神经系统（CNS）由高度异质的神经元和神经胶质细胞群体组成，聚集在具有特定功能的不同解剖区域，但仍有一些情况，包括警觉、意识和注意力，需要大脑大面积区域内同时、协调且空间均匀的活动。在这些事件中，大脑仅占体重的约2%，但在静息时消耗身体五分之一的葡萄糖，需要产生额外的能量。大脑相对较大区域内如何同时进行能量获取，目前了解甚少。这种机制在神经退行性疾病中可能受损，例如在阿尔茨海默病中，其标志是大脑代谢减退。星形胶质细胞是大脑中产生和储存糖原（一种能量形式）的主要神经细胞类型，也是中枢神经系统代谢和稳态支持的关键，并且在神经退行性变中受损，导致大脑中兴奋 - 能量耦合的缓慢下降。许多机制都受到影响，包括细胞间信号传导。一个重要的问题是，在相当短的时间范围内发生的细胞信号变化，如何导致数十年发展起来的神经退行性变。在这篇综述中，我们首先关注阿尔茨海默病的缓慢动态变化，以及蓝斑核（一个参与觉醒的脑干核团）的活动。随后，我们概述囊泡运输和胞质钙动力学等快得多的过程，这两者在健康和神经退行性变中都塑造了星形胶质细胞 - 神经元通讯的信号格局。
