Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice

IF 4.7 2区医学 Q1 NEUROIMAGING NeuroImage Pub Date : 2024-09-25 DOI:10.1016/j.neuroimage.2024.120860

Laura M. Bartos , Sebastian T. Kunte , Stephan Wagner , Philipp Beumers , Rebecca Schaefer , Artem Zatcepin , Yunlei Li , Maria Griessl , Leonie Hoermann , Karin Wind-Mark , Peter Bartenstein , Sabina Tahirovic , Sibylle Ziegler , Matthias Brendel , Johannes Gnörich

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Abstract

Purpose

2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood.

Methods

Healthy wild-type mice of both sexes (2–21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons. Cerebral FDG uptake and metabolic connectivity were determined by PET. A subset of mice received measurement of blood glucose levels to study associations with cellular FDG uptake during aging.

Results

Cerebral FDG-PET signals in healthy mice increased linearly with age. Cellular FDG uptake of neurons increased between 2 and 12 months of age, followed by a strong decrease towards late ages. Contrarily, FDG uptake in microglia and astrocytes exhibited a U-shaped function with respect to age, comprising the predominant cellular source of higher cerebral FDG uptake in the later stages. Metabolic connectivity was closely associated with the ratio of glucose uptake in astroglial cells relative to neurons. Cellular FDG uptake was not associated with blood glucose levels and increasing FDG brain uptake as a function of age was still observed after adjusting for blood glucose levels.

Conclusion

Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.

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星状胶质细胞葡萄糖摄取决定小鼠健康衰老过程中大脑 FDG-PET 改变和代谢连接。

目的：2-氟脱氧葡萄糖-PET（FDG-PET）是研究哺乳动物大脑中葡萄糖代谢的有力工具，但目前还不清楚衰老过程中葡萄糖摄取的细胞来源和代谢连接性。方法：健康的野生型小鼠（2-21 个月大）雌雄均可接受 FDG-PET，并在体内注射示踪剂（scRadiotracing）后进行细胞分选。对离体小胶质细胞、星形胶质细胞和神经元每个细胞的 FDG 摄取量进行量化。通过 PET 测定大脑 FDG 摄取量和代谢连接性。一部分小鼠接受了血糖水平测量，以研究衰老过程中细胞 FDG 摄取的相关性：结果：健康小鼠的大脑 FDG-PET 信号随年龄呈线性增长。神经元的细胞 FDG 摄取量在 2 到 12 个月大时增加，随后在晚期大幅下降。与此相反，小胶质细胞和星形胶质细胞的 FDG 摄取量随年龄呈 U 型变化，是后期大脑 FDG 摄取量较高的主要细胞来源。代谢连通性与星形胶质细胞相对于神经元的葡萄糖摄取比率密切相关。细胞FDG摄取量与血糖水平无关，在调整血糖水平后，仍可观察到大脑FDG摄取量随年龄增长而增加：结论：星状胶质细胞葡萄糖摄取的轨迹推动了大脑 FDG-PET 的改变以及衰老过程中的代谢连接。

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来源期刊

NeuroImage 医学-核医学

CiteScore

11.30

自引率

10.50%

发文量

809

审稿时长

63 days

期刊介绍： NeuroImage, a Journal of Brain Function provides a vehicle for communicating important advances in acquiring, analyzing, and modelling neuroimaging data and in applying these techniques to the study of structure-function and brain-behavior relationships. Though the emphasis is on the macroscopic level of human brain organization, meso-and microscopic neuroimaging across all species will be considered if informative for understanding the aforementioned relationships.