Metabolic Mapping with (14C)-2-Deoxyglucose and (14C)- Glucose

提出了对(14C)-2-脱氧葡萄糖和特殊标记的(14C)-葡萄糖在测量脑功能活动中的使用进行关键评估的实验。将用高分辨率放射自显影技术评估(14C)-2-脱氧葡萄糖、(1-14C)-葡萄糖和(6-14C)-葡萄糖在不同脑区的放射性摄取和滞留情况。这些研究将描绘不同化合物对放射性的相对摄取和保留以及用适当的动力学模型确定的葡萄糖利用率的异同。这一假设将被检验，即先前证明的来自(14C)-2-DG的放射性在某些脑区相对于来自(1-14C)-葡萄糖的低保留是由于局部高的葡萄糖-6-磷酸酶活性，低的2-DG的磷酸化，或低转运的(14C)-2-脱氧葡萄糖-6-磷酸积聚将在显微解剖的脑区通过液体闪烁计数来测量，在静脉注射后1-45分钟的大鼠。注射(14C)-脱氧葡萄糖。如果大脑的某些区域含有较高的葡萄糖-6-磷酸活性，就会出现最初的蓄积，然后是2-脱氧葡萄糖-6-磷酸的下降。如果大脑区域表现出(14C)-2-DG的低磷酸化，则(14C)-2-DG的少量积累不像葡萄糖那样有效地输送到特定区域的细胞中，则(14C)-2-DG的放射性积累水平将始终较低。(14C)-2-DG和特殊标记的(14C)-葡萄糖记录功能活动变化的能力将由感觉刺激和刺激到海马结构的明确的传入通路来确定。同时进行电生理记录，以确定代谢和电活动的关系。

Experiments are proposed to provide a critical assessment of the use of (14C)-2-deoxglucose and specifically labeled (14C)-glucose in the measurement of cerebral functional activity. The uptake and retention of radioactivity in discrete brain regions from (14C)-2-deoxyglucose, (1-14C)-glucose and (6-14C)-glucose will be evaluated with high resolution autoradiography in which 4 um frozen brain sections are thaw-mounted onto nuclear emulsion coated slides. These studies will delineate the similarities and differences in the relative uptake and retention of radioactivity from the various compounds and in glucose utilization rates determined with the appropriate kinetic models. The hypothesis will be tested that the previously demonstrated low retention of radioactivity from (14C)-2-DG in some brain regions relative to that from (1-14C)-glucose is due to regionally high glucose-6- phosphatase activity, low phosphorylation of 2-DG, or low transport of (14C)-2-deoxyglucose-6- phosphate accumulation will be measured in microdissected brain regions by liquid scintillation counting in rats killed by microwave radiation, 1 to 45 minutes after i.v. injection of (14C)-deoxyglucose. If some brain regions contain high glucose-6-phosphate activity, an initial accumulation, followed by a decline in 2-deoxyglucose-6- phosphate, is predicted. If a brain region exhibits low phosphorylation of (14C)-2-DG, little accumulation of (14C)-2-DG is not transported as effectively into the cells of certain regions as is glucose, low levels of accumulation of radioactivity from (14C)-2-DG will occur at all times. The ability of (14C)-2-DG and specifically labelled (14C)-glucose to register alterations in functional activity will be determined by sensory stimulation and by stimulating a well defined afferent pathway to the hippocampal formation. Concurrent electrophysiological recording will be performed to determine the relationship of metabolic and electrical activities.