Christopher Wolff, Dorit John, Ulrike Winkler, Luise Hochmuth, Johannes Hirrlinger, Susanne Köhler
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Utilizing genetically encoded, fluorescent nanosensors, the cytosolic concentrations of glucose, lactate, and ATP, along with glycolytic rate and the NADH/NAD<sup>+</sup> redox state were measured. Under basal conditions, differences between the two populations of astrocytes were observed for glucose and lactate concentrations as well as the glycolytic rate. Additionally, astrocytic metabolism responded to insulin and leptin in both brain regions, with some unique characteristics for each cell population. Finally, both hormones influenced how cells responded to elevated extracellular levels of potassium ions, a common indicator of neuronal activity. In summary, our study provides evidence that insulin and leptin acutely regulate astrocytic metabolism within minutes. 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引用次数: 0
摘要
星形胶质细胞是大脑中的一个异质性细胞群,对大脑的平衡起着至关重要的作用,并在大脑的整体功能中扮演着重要角色。星形胶质细胞的功能和新陈代谢不仅受附近神经元等局部信号的调节,还受激素等远距离信号的调节。因此,两种主要调节整个机体能量平衡的重要激素--胰岛素和瘦素,据报道也会影响脑内的星形胶质细胞。在这项研究中,我们研究了这些激素对小鼠大脑皮层和下丘脑(营养调节的关键区域)中培养的星形胶质细胞新陈代谢的急性调节。利用基因编码的荧光纳米传感器,测量了细胞膜中葡萄糖、乳酸和 ATP 的浓度,以及糖酵解率和 NADH/NAD+ 氧化还原状态。在基础条件下,观察到两组星形胶质细胞的葡萄糖和乳酸浓度以及糖酵解率存在差异。此外,两个脑区的星形胶质细胞代谢对胰岛素和瘦素都有反应,每个细胞群都有一些独特的特征。最后,这两种激素都会影响细胞对细胞外钾离子水平升高的反应,而钾离子是神经元活动的常见指标。总之,我们的研究提供了证据,证明胰岛素和瘦素可在几分钟内调节星形胶质细胞的新陈代谢。此外,虽然下丘脑和大脑皮层的星形胶质细胞在新陈代谢方面有相似之处,但它们也表现出不同的特性,这进一步强调了人们对星形胶质细胞异质性的日益认识。
Insulin and leptin acutely modulate the energy metabolism of primary hypothalamic and cortical astrocytes.
Astrocytes constitute a heterogeneous cell population within the brain, contributing crucially to brain homeostasis and playing an important role in overall brain function. Their function and metabolism are not only regulated by local signals, for example, from nearby neurons, but also by long-range signals such as hormones. Thus, two prominent hormones primarily known for regulating the energy balance of the whole organism, insulin, and leptin, have been reported to also impact astrocytes within the brain. In this study, we investigated the acute regulation of astrocytic metabolism by these hormones in cultured astrocytes prepared from the mouse cortex and hypothalamus, a pivotal region in the context of nutritional regulation. Utilizing genetically encoded, fluorescent nanosensors, the cytosolic concentrations of glucose, lactate, and ATP, along with glycolytic rate and the NADH/NAD+ redox state were measured. Under basal conditions, differences between the two populations of astrocytes were observed for glucose and lactate concentrations as well as the glycolytic rate. Additionally, astrocytic metabolism responded to insulin and leptin in both brain regions, with some unique characteristics for each cell population. Finally, both hormones influenced how cells responded to elevated extracellular levels of potassium ions, a common indicator of neuronal activity. In summary, our study provides evidence that insulin and leptin acutely regulate astrocytic metabolism within minutes. Additionally, while astrocytes from the hypothalamus and cortex share similarities in their metabolism, they also exhibit distinct properties, further underscoring the growing recognition of astrocyte heterogeneity.
期刊介绍:
Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.