Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany.
Neuroimage. 2024 Oct 15;300:120860. doi: 10.1016/j.neuroimage.2024.120860. Epub 2024 Sep 25.
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.
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.
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.
Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.
2-氟脱氧葡萄糖-PET（FDG-PET）是研究哺乳动物大脑葡萄糖代谢的有力工具，但在衰老过程中，细胞摄取葡萄糖的来源和代谢连接尚不清楚。
健康的野生型雌雄小鼠（2-21 月龄）在体内示踪剂注射后接受 FDG-PET 和细胞分选（scRadiotracing）。在分离的小胶质细胞、星形胶质细胞和神经元中定量测定细胞内 FDG 摄取量。通过 PET 测定脑 FDG 摄取和代谢连接。对一部分小鼠进行血糖水平测量，以研究衰老过程中细胞 FDG 摄取与血糖之间的关系。
健康小鼠的脑 FDG-PET 信号随年龄呈线性增加。神经元的细胞 FDG 摄取在 2 至 12 月龄之间增加，随后在老年时急剧下降。相反，小胶质细胞和星形胶质细胞的 FDG 摄取与年龄呈 U 形关系，构成了老年阶段大脑 FDG 摄取较高的主要细胞来源。代谢连接与星形胶质细胞相对神经元的葡萄糖摄取比值密切相关。细胞 FDG 摄取与血糖水平无关，并且在调整血糖水平后，仍观察到年龄增长导致的脑 FDG 摄取增加。
星形胶质细胞摄取葡萄糖的轨迹驱动着衰老过程中大脑 FDG-PET 的改变和代谢连接。
