Cerebral Glucose Utilization: Comparison of [¹⁴C]Deoxyglucose and [6‐¹⁴C]Glucose Quantitative Autoradiography

Abstract

The [14C]deoxyglucose [Sokoloff et al., J. Neurochem. 28, 897-916 (1977)] and [6-14C]glucose [Hawkins et al., Am. J. Physiol. 248, C170-C176 (1985)] quantitative autoradiographic methods were used to measure regional brain glucose utilization in awake rats. The spatial resolution and qualitative appearance of the autoradiograms were similar. In resting animals, there was no significant difference between the two methods among 18 gray and three white matter structures over a fourfold range in glucose utilization rates (coefficient of correlation = 0.97). In rats given increasing frequencies of photoflash visual stimulation, the two methods gave different results for glucose utilization within visual pathways. The linearity of the metabolic response was studied in the superior colliculus using an on-off checkerboard stimulus between 0 and 33 Hz. The greatest increment in activity occurred between 0 and 4 Hz stimulation with both methods, probably representing recruitment of neuronal elements into activity. Above 4 Hz, there was a progressive increase in labeling with [14C]deoxyglucose up to 1.7 times control at 33 Hz. With [6-14C]-glucose, there was no further increment in change above a 30% increase seen at 4 Hz. Measurement of tissue glucose revealed no drop in the visually stimulated structures compared to control. We interpret these results to indicate that, with increasing rates of physiological activity, the products of deoxyglucose metabolism accumulate progressively, but the products of glucose metabolism are removed from brain in 10 min.

Comparison of Cerebral Glucose Metabolic Rates Measured with Fluorodeoxyglucose and Glucose Labeled in the 1, 2, 3–4, and 6 Positions Using Double Label Quantitative Digital Autoradiography

“…This observation suggests that conditions which could cause increases in LCMR g 1u to above normal levels might be even less accu rately depicted by glucose. Recent observations that visual stimulation produced twofold increases in LCMR g 1u in some brain structures as determined with DG, compared to only 30% with [6-14C]glu cose, agree with this prediction (Collins et al, 1987).…”

Cortical metabolic rates as measured by 2-deoxyglucose-uptake are increased after waking and decreased after sleep in mice

“…The stability of 2-DG in the brain tissue, however, is less than previously assumed [30], since it has been shown that 10 min after the injection 2-DG is lost from the brain at a significant rate [11,12]. In any case, the direct comparison of metabolic rates assessed by the 2-DG and 14 C-glucose consumption revealed close correspondence between the two methods for many brain regions [9,10], and 2-DG appears to be a more sensitive marker of regional functional activation after sensory stimulation compared to 14 Cglucose [7][8][9]. Furthermore, the use of 2-DG enabled us to compare our results with previous reports [26,30,35].…”

Trafficking of Glucose, Lactate, and Amyloid-β from the Inferior Colliculus through Perivascular Routes

“…Discordant results obtained with [6- 14 C]glucose and [ 14 C]deoxyglucose were hypothesized to arise from upregulation of glycolysis, with increased [ 14 C]lactate production and release from activated structures (Fig. 1A) (Collins et al, 1987; Ackermann and Lear, 1989; Lear and Ackermann, 1989; Lear, 1990), a concept supported by rapid efflux of [ 14 C]lactate to blood during spreading cortical depression (Adachi et al, 1995; Cruz et al, 1999). Spreading and release of [ 14 C]glucose-derived label during acoustic activation of the inferior colliculus is reduced by inhibition of lactate transporters and astrocytic gap junctions (Cruz et al, 2007), supporting the importance of lactate release and implicating astrocytes in metabolite dispersal.…”

“…However, incomplete product trapping due to rapid release from activated tissue of labeled metabolites derived from [1- or 6- 14 C]glucose (Fig. 1A) causes underestimation (≥50%) of functional activation in different brain structures under normal stimulatory conditions compared to parallel studies with [ 14 C]deoxyglucose, which is metabolized mainly to [ 14 C]deoxyglucose-6-phosphate that is trapped intracellularly and not further metabolized by the glycolytic pathway (Sokoloff et al, 1977); undetected losses of labeled glucose metabolites also affects interpretation of results obtained under pathophysiological conditions, e.g., when excitatory activity is not reflected by label accumulation (Collins et al, 1987; Ackermann and Lear, 1989; Adachi et al, 1995; Cruz et al, 1999; Cruz et al, 2007). Discordant results obtained with [6- 14 C]glucose and [ 14 C]deoxyglucose were hypothesized to arise from upregulation of glycolysis, with increased [ 14 C]lactate production and release from activated structures (Fig.…”