Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.

Takahashi, Shinichi; Driscoll, Bernard F.; Law, Mona J.; Sokoloff, Louis

doi:10.1073/pnas.92.10.4616

Cited by 173 publications

(178 citation statements)

References 48 publications

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“…It is widely reported that neurons in vitro consume more glucose than cultured astroglia (Brookes and Yarowsky, 1985;Itoh et al, 2003b;Takahashi et al, 1995). Therefore, we did not compare the glucose phosphorylation rate between neurons and astroglia in vitro with 2-NBDG in the present study.…”

Section: Discussionmentioning

confidence: 99%

Fluorometric Determination of Glucose Utilization in Neurons in Vitro and in Vivo

Itoh

Abe

Takaoka

et al. 2004

J Cereb Blood Flow Metab

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Summary:Glucose is the major energy source the adult brain utilizes under physiologic conditions. Recent findings, however, have suggested that neurons obtain most of their energy from the oxidation of extracellular lactate derived from astroglial metabolism of glucose transported into the brain from the blood. In the present studies we have used 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent analogue of 2-deoxyglucose, which is often used to trace glucose utilization in neural tissues, to examine glucose metabolism in neurons in vitro and in vivo. Cultured neurons and astroglia were incubated with 2-NBDG for up to 15 minutes, and nonmetabolized 2-NBDG was washed out. We found that fluorescence intensity increased linearly with incubation time in both neurons and astroglia, indicating that both types of brain cells could utilize glucose as their energy source in vitro. To determine if the same were true in vivo, Sprague-Dawley rats were injected intravenously with a pulse bolus of 2-NBDG and decapitated 45 minutes later. Examination of brain sections demonstrated that phosphorylated 2-NBDG accumulated in hippocampal neurons and cerebellar Purkinje cells, indicating that neurons can utilize glucose in vivo as energy source.

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Section: Discussionmentioning

confidence: 99%

Fluorometric Determination of Glucose Utilization in Neurons in Vitro and in Vivo

Itoh

Abe

Takaoka

et al. 2004

J Cereb Blood Flow Metab

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“…The importance of oxidative phosphorylation for EPSC recovery after a strong presynaptic stimulus could implicate the astrocyte-neuron lactate shuttle (Pellerin and Magistretti, 1994;Takahashi et al, 1995;Bittner et al, 2010). However, neither pharmacological inhibition of monocarboxylate transport (Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential Presynaptic ATP Supply for Basal and High-Demand Transmission

Sobieski¹,

Fitzpatrick

Mennerick

2017

J. Neurosci.

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The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of both ATP sources abolished evoked transmission. Neither action potential propagation failure nor depressed Ca 2ϩ influx explained loss of evoked synaptic transmission. Rather, inhibition of ATP synthesis caused massive spontaneous vesicle exocytosis, followed by arrested endocytosis, accounting for the disappearance of evoked postsynaptic currents. In contrast to its weak effects on basal transmission, inhibition of oxidative phosphorylation alone depressed recovery from vesicle depletion. Local astrocytic lactate shuttling was not required. Instead, either ambient monocarboxylates or neuronal glycolysis was sufficient to supply requisite substrate. In summary, basal transmission can be sustained by glycolysis, but strong presynaptic demands are met preferentially by oxidative phosphorylation, which can be maintained by bulk but not local monocarboxylates or by neuronal glycolysis.

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“…If half of the glucose is metabolized in astrocytes, then increased oxidative metabolism produces a similar amount of ATP as the increase in glycolysis. If all glycolytic ATP were used to Brain lactate metabolism GA Dienel +15 to +180 +40 to +55 Pellerin and Magistretti, 1994;Takahashi et al, 1995;Debernardi et al, 1999;Chatton et al, 2003 10-1,000…”

Section: Brain Activation In Vivo Activates Glycogenolysis and Oxidatmentioning

confidence: 99%

Brain Lactate Metabolism: The Discoveries and the Controversies

Dienel

2011

J Cereb Blood Flow Metab

416

434

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Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-toblood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an 'opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. Keywords: astrocyte; brain activation; glucose; lactate shuttling; metabolism; neuron Glucose is the major fuel for the brain, and its metabolism by different pathways has important functions related to energetics, neurotransmission, oxidation-reduction (redox) reactions, and biosynthesis of essential brain components (Figure 1). For many decades, lactate production in the brain was viewed as a consequence of inadequate oxygen delivery, disruption of oxidative metabolism, or mismatch between glycolytic and oxidative rates (Siesjö, 1978), but more recently, the conceptual role of lactate metabolism and function in the normal brain have undergone major changes, shifting from developmental fuel and glycolytic waste product to include its use as a supplemental fuel and signaling molecule. Starting in the 1970s to 1980s studies carried out in different laboratories with diverse experimental interests related to brain function brought attention to upregulation of glycolysis, lactate production, lactate release into the blood, the possibility of lactate shuttling among cell types within the brain, lactate fueling adult brain during exercise, and roles of lactate in the regulation of blood flow; some of these topics are controversial and highly debated. The experimental paradigm and physiologic status of subjects are critical for interpretation of data, and this review first presents a brief historical overview of studies related to brain lactate transport and metabolism, then compares sets of data to provide a perspective and context within which the consistency of simi...

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Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.

Abstract: ABSTRACT

Cited by 173 publications

References 48 publications

Fluorometric Determination of Glucose Utilization in Neurons in Vitro and in Vivo

Fluorometric Determination of Glucose Utilization in Neurons in Vitro and in Vivo

Differential Presynaptic ATP Supply for Basal and High-Demand Transmission

Brain Lactate Metabolism: The Discoveries and the Controversies

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