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

(14C)-2-脱氧葡萄糖和 (14C)-葡萄糖的代谢图谱

• 批准号: 8721777
• 负责人: Gary Duncan
• 金额: $ 2万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1989-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8721777&HistoricalAwards=false
• 关键词: Metabolic; Mapping; 14C; Deoxyglucose; Glucose

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.

实验提出了一个关键的评估 （14 C）-2-脱氧葡萄糖和特异性标记的（14 C）-葡萄糖的用途 大脑功能活动的测量。 摄取 以及放射性在大脑中的分布 （14 C）-2-脱氧葡萄糖、（1- 14 C）-葡萄糖和（6- 14 C）-葡萄糖将被 用高分辨率放射自显影进行评价，其中4 μ m 将冷冻的脑切片解冻固定在核乳胶上 包被载玻片。 这些研究将描述相似之处， 放射性相对摄取和保留的差异 从各种化合物和葡萄糖利用率 用适当的动力学模型确定。 的假设 将测试先前证明的低保留率， （14 C）-2-DG在某些脑区的放射性相对于 来自（1- 14 C）-葡萄糖的是由于区域性高葡萄糖-6- 磷酸酶活性，2-DG磷酸化低，或 （14 C）-2-脱氧葡萄糖-6-磷酸积累的转运将 在显微解剖的大脑区域中通过液体测量 微波辐射致死大鼠的闪烁计数， 至静脉注射（14 C）-脱氧葡萄糖后45分钟。 如果 一些脑区含有高葡萄糖-6-磷酸活性， 最初的积累，其次是2-脱氧葡萄糖-6- 磷酸盐，预测。 如果一个大脑区域表现出低 （14 C）-2-DG磷酸化，（14 C）-2-DG几乎不蓄积 并不能有效地运输到某些 区域是葡萄糖，低水平的积累， （14 C）-2-DG的放射性将一直存在。 的 （14 C）-2-DG和特异性标记的（14 C）-葡萄糖 功能活动中的寄存器变更将由 感觉刺激和通过刺激一个明确的传入 海马结构的通路。 并发 将进行电生理记录以确定 代谢和电活动的关系。