Predominant Enhancement of Glucose Uptake in Astrocytes versus Neurons during Activation of the Somatosensory Cortex

Abstract

Glucose is the primary energetic substrate of the brain, and measurements of its metabolism are the basis of major functional cerebral imaging methods. Contrary to the general view that neurons are fueled solely by glucose in proportion to their energetic needs, recent in vitro and ex vivo analyses suggest that glucose preferentially feeds astrocytes. However, the cellular fate of glucose in the intact brain has not yet been directly observed. We have used a real-time method for measuring glucose uptake in astrocytes and neurons in vivo in male rats by imaging the trafficking of the nonmetabolizable glucose analog 6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-aminoglucose (6-NBDG) using two-photon microscopy. During resting conditions we found that astrocytes and neurons both take up 6-NBDG at the same rate in the barrel cortex of the rat. However, during intense neuronal activity triggered by whisker stimulation, astrocytes rapidly accelerated their uptake, whereas neuronal uptake remained almost unchanged. After the stimulation period, astrocytes returned to their preactivation rates of uptake paralleling the neuronal rate of uptake. These observations suggest that glucose is taken up primarily by astrocytes, supporting the view that functional imaging experiments based on glucose analogs extraction may predominantly reflect the metabolic activity of the astrocytic network.

Endothelial Cell-Derived Nitric Oxide Enhances Aerobic Glycolysis in Astrocytes via HIF-1 -Mediated Target Gene Activation

“…At rest, astrocytes have a higher glycolytic activity than neurons, an observation which is supported by results obtained with transcriptomic analysis on acutely isolated cells indicating a predominant expression of genes encoding glycolytic enzymes in astrocytes versus neurons (Rossner et al, 2006;Lovatt et al, 2007;Cahoy et al, 2008). In addition, recent results in vivo also suggest that astrocytes, in contrast to neurons, respond to neuronal activation by exhibiting a predominant glycolytic response (Chuquet et al, 2010). Whether such a distinctive feature depends only on a constitutive difference in expression of genes encoding glycolytic enzymes or whether it can be further reinforced by external signals was so far unknown.…”

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

“…These observations may also provide insight into the reason why astrocytes can sustain a higher basal glycolytic rate than neurons, and why neurons depend on astrocytes to meet their energy needs-as proposed by the ANLS model and substantiated by several in vitro, ex vivo, and in vivo data (Kasischke et al, 2004;Porras et al, 2004;Rouach et al, 2008;Magistretti, 2009;Chuquet et al, 2010). Considering that glucose metabolism inevitably leads to MG formation, lactate utilization may provide a means for neurons to alleviate MG toxicity by decreasing their glucose utilization, yet meet their high energetic requirements by using astrocyte-derived lactate, which can be oxidized in the Krebs cycle following its conversion to pyruvate.…”

Age-Dependent Rescue by Simvastatin of Alzheimer's Disease Cerebrovascular and Memory Deficits

“…Both responses require astrocytes as intermediaries either for glucose uptake (Chuquet et al, 2010) or calcium signaling and release of vasodilatory mediators (Koehler et al, 2009). Simvastatin attenuated astrocyte activation in the cortex where the CGU and CBF responses were recorded, and reduced the number of ROSproducing NADPH/p22 phox subunit-positive glial cells (Tong et al, 2009).…”