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Cellular Origin of [18F]FDG-PET Imaging Signals During Ceftriaxone-Stimulated Glutamate Uptake: Astrocytes and Neurons.
The Neuroscientist ( IF 5.6 ) Pub Date : 2017-12-24 , DOI: 10.1177/1073858417749375
Gerald A Dienel 1, 2 , Kevin L Behar 3 , Douglas L Rothman 4
Affiliation  

Ceftriaxone stimulates astrocytic uptake of the excitatory neurotransmitter glutamate, and it is used to treat glutamatergic excitotoxicity that becomes manifest during many brain diseases. Ceftriaxone-stimulated glutamate transport was reported to drive signals underlying [18F]fluorodeoxyglucose-positron emission tomographic ([18F]FDG-PET) metabolic images of brain glucose utilization and interpreted as supportive of the notion of lactate shuttling from astrocytes to neurons. This study draws attention to critical roles of astrocytes in the energetics and imaging of brain activity, but the results are provocative because (1) the method does not have cellular resolution or provide information about downstream pathways of glucose metabolism, (2) neuronal and astrocytic [18F]FDG uptake were not separately measured, and (3) strong evidence against lactate shuttling was not discussed. Evaluation of potential metabolic responses to ceftriaxone suggests lack of astrocytic specificity and significant contributions by pre- and postsynaptic neuronal compartments. Indeed, astrocytic glycolysis may not make a strong contribution to the [18F]FDG-PET signal because partial or complete oxidation of one glutamate molecule on its uptake generates enough ATP to fuel uptake of 3 to 10 more glutamate molecules, diminishing reliance on glycolysis. The influence of ceftriaxone on energetics of glutamate-glutamine cycling must be determined in astrocytes and neurons to elucidate its roles in excitotoxicity treatment.



中文翻译:

在头孢曲松刺激的谷氨酸摄取过程中 [18F] FDG-PET 成像信号的细胞起源:星形胶质细胞和神经元。

头孢曲松刺激兴奋性神经递质谷氨酸的星形胶质细胞摄取,并用于治疗在许多脑部疾病中表现出来的谷氨酸能兴奋性毒性。据报道,头孢曲松刺激的谷氨酸转运可驱动脑葡萄糖利用的[ 18 F] 氟脱氧葡萄糖 - 正电子发射断层扫描 ([ 18 F] FDG-PET) 代谢图像背后的信号,并被解释为支持乳酸从星形胶质细胞穿梭到神经元的概念。这项研究提请注意星形胶质细胞在大脑活动的能量学和成像中的关键作用,但结果具有启发性,因为 (1) 该方法没有细胞分辨率或提供有关葡萄糖代谢下游途径的信息,(2) 神经元和星形胶质细胞[ 18F] FDG 摄取没有单独测量,并且 (3) 没有讨论反对乳酸穿梭的有力证据。对头孢曲松潜在代谢反应的评估表明缺乏星形胶质细胞特异性和突触前和突触后神经元区室的显着贡献。事实上,星形胶质细胞糖酵解可能不会对 [ 18 F]FDG-PET 信号做出很大贡献,因为一个谷氨酸分子在其摄取时部分或完全氧化会产生足够的 ATP 来促进 3 到 10 个更多谷氨酸分子的摄取,从而减少对糖酵解的依赖. 必须在星形胶质细胞和神经元中测定头孢曲松对谷氨酸-谷氨酰胺循环能量学的影响,以阐明其在兴奋性毒性治疗中的作用。

更新日期:2017-12-24
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