Cellular pathways of energy metabolism in the brain: Is glucose used by neurons or astrocytes?

Abstract

Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified.

Energy Metabolism in Huntington’s Disease

“…On the contrary, neurons contribute minimally to glucose consumption by the brain. Thus, despite their shared localization, neurons and astrocytes exhibit a different preference for glucose consumption and utilization (Nehlig and Coles, 2007).…”

“…One interesting, however somehow surprising, observation made by different laboratories is the fact that, in contrast to astrocytes, neurons do not display increased glycolytic rate upon mitochondrial inhibition as one could expect (Bolanos et al, 2008;Bolanos et al, 2010), but instead these neuronal cells entry into cell death program. These results lead us to assume that the increased glycolytic rate in astrocytes served to preserve cells from ATP depletion and cell death, most probably because glycolytic ATP was used to drive the reverse activity of ATP synthase to maintain the mitochondrial membrane potential (Nehlig and Coles, 2007;Bolanos et al, 2010;Cunnane et al, 2011). On the other hand, such treatment caused neuronal ATP depletion and apoptotic cell death (Nehlig and Coles, 2007).…”

“…These results lead us to assume that the increased glycolytic rate in astrocytes served to preserve cells from ATP depletion and cell death, most probably because glycolytic ATP was used to drive the reverse activity of ATP synthase to maintain the mitochondrial membrane potential (Nehlig and Coles, 2007;Bolanos et al, 2010;Cunnane et al, 2011). On the other hand, such treatment caused neuronal ATP depletion and apoptotic cell death (Nehlig and Coles, 2007). Based on all facts presented so far one can hypothesize that neurodegenerative diseases (including Alzheimer's Disease and Huntington's Disease) may present a diminished neuronal glycolytic activity (Oliveira et al, 2007).…”

GLP-2 potentiates L-type Ca2+ channel activity associated with stimulated glucose uptake in hippocampal neurons

“…In the mammalian brain, ϳ50% of the total energy consumption is associated with neural signaling, including maintenance of resting potentials and neurotransmitter recycling (2,46). In the brain, glucose is the predominant substrate for energy metabolism.…”

Glucose Transporter Distribution in the Vessels of the Central Nervous System of the Axolotl Ambystoma mexicanum (Urodela: Ambystomatidae)

“…In fact, endothelial cells have transporter proteins that supply the nervous tissue with the essential substances that are stopped by the blood-neuropilar fluid passive diffusion barrier (Risau et al, 1986;Dermietzel and Krause, 1991). The development and maturation of the CNS, as well as its physiological functions in the mature state, depend on a constant and undisturbed supply of glucose, which is the major source of energy for the nervous tissue (Cornford et al, 1993;Bolz et al, 1996;Tabernero et al, 2006;Barros et al, 2007;Brown and Ransom, 2007;Nehlig and Coles, 2007;Simpson et al, 2007). The transport of D-glucose into the CNS is saturable, stereospecific, and does not depend on the energy supply (Pardridge et al, 1990;Farrell and Pardridge, 1991;Bell et al, 1993).…”