Synthesis of transmitter glutamate and the glial-neuron interrelationship

Torgner, Ingeborg Aa.; Kvamme, Elling

doi:10.1007/bf03160053

Cited by 29 publications

(15 citation statements)

References 29 publications

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“…One possible explanation of the third phenomenon (i.e., tendency of the dialysate glutamate concentration to decrease despite the DC potential showing similar negative shifts) is that one glutamate pool, possibly the neurotransmitter pool (Ca 2+ -dependent exocytotic release), has been partly depleted by the previous severe ischemic insults. The fact that glutamate released presynaptically is reuptaken by both neurons and glial cells, and specifically metabolized in glial cells, 29 supports this hypothesis.…”

supporting

confidence: 66%

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Ueda

Obrenovitch

Lok

et al. 1992

Stroke

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Background and Purpose: Evidence suggesting that ischemia-induced neuronal damage may be linked to an extracellular overflow of glutamate has accumulated, and previous studies have shown that repetitive ischemic insults may have a cumulative effect. The purpose of this study was to investigate changes in the extracellular glutamate concentration produced by repeated brief ischemic episodes of varied severity.Methods: Four consecutive 3-or 5-minute periods of bilateral hemispheric ischemia were produced in rats, each ischemic period followed by 27 minutes of reperfusion. Extracellular glutamate in the striatum was monitored using microdialysis, and the electroencephalogram and extracellular direct current potential were recorded in the same tissue site to assess the severity of ischemia.Results: The results suggest that the kinetics of the increase in the extracellular glutamate concentration produced by a brief ischemic episode are similar, irrespective of whether it is a single insult or part of a repeated sequence. In all cases, the extracellular glutamate concentration increased throughout ischemia and returned to its preischemic level early during reperfusion. The pattern of changes in the ischemiainduced glutamate overflow during repetitive insults varied with the severity of ischemia, in common with the pattern of changes in the direct current potential, supporting the concept that ionic changes associated with anoxic depolarization are a major determinant of ischemia-induced glutamate overflow.Conclusions: There may be no cumulative effect of brief repeated episodes of ischemia on the extracellular glutamate concentration, even though repeated 5-minute ischemic episodes apparently caused progressive deterioration of ionic homeostasis in some cases. (Stroke 1992;23:1125-1131 KEY WORDS • cerebral ischemia • electroencephalography • glutamate • rats

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supporting

confidence: 66%

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Ueda

Obrenovitch

Lok

et al. 1992

Stroke

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“…Glial pyruvate carboxylation and glutamine synthesis, attributed to the replenishment of neuronal glutamate, contribute significantly to the interplay between cerebral glucose metabolism and glutamatergic neurotransmission. 20,11,[30][31][32][33][34] It is well established now that the glutamine-glutamate cycle is not stoichiometric. 18 The operation of the glutamate-glutamine cycle requires that the fluxes, distribution and interconversion between glucose, glutamate and glutamine must be flexible to changes in neuronal activity, and a variety of mechanisms may contribute to such homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…20,11,[30][31][32][33][34] GS activity in cultured astrocytes has been observed to be closely correlated with the increasing activity of this enzyme in vivo in developing brain. Furthermore, glutamine de novo synthesis, as well as GS mRNA and activity, increased markedly in astrocytes co-cultured with neurons.…”

mentioning

confidence: 96%

Regulation of glial metabolism studied by ¹³C‐NMR

Zwingmann¹,

Leibfritz²

2003

NMR in Biomedicine

106

107

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Glial metabolism and their metabolic trafficking with neurons are essential parts of neuronal function, as they modulate, by this means, neuronal activity. Ex vivo and in vitro 13 C-NMR spectroscopy have been used to monitor neural cellular and tissue metabolism. Special emphasis has been given to the metabolic specialization of astrocytes and its enzymatic regulation. For this purpose primary cell cultures are useful tools to study neuronal-glial metabolic relationships as the extracellular fluid can be investigated and manipulated by various stimuli. In astrocytes, glucose is utilized predominantly anaerobically. Glycolysis is interrelated to the astrocytic TCA cycle via bi-directional signals and metabolic exchange processes between astrocytes and neurons. Besides glucose oxidation, neuronally released glutamate is metabolized through the glial TCA cycle. The flexibility of glutamate metabolism, depending on ammonia and energy homeostasis, and the discovered pyruvate recycling pathway in astrocytes, modulates the glutamine-glutamate cycle. 13 C-NMR studies have extended the concept of the 'non-stoichiometric' glutamate-glutamine cycle between neurons and astrocytes. An alanine-lactate shuttle between neurons and astrocytes contributes to nitrogen transfer from neurons to astrocytes, recycles energy substrates for neurons, and in return promotes intercellular glutamine-glutamate cycling. The conversion of alanine to lactate in astrocytes is regulated by intracytosolic pyruvate compartmentation. In essence, the metabolic flexibility and compartmentalized enzymatic specialization of astrocytes buffers the brain tissue against metabolic impairments and excitotoxicity in response to extracellular stimuli, some of them being released by neurons. These in vitro studies using 13 C-NMR spectroscopy provide important knowledge regarding physiological and pathophysiological regulation of neural metabolism to improve our understanding of general brain function.

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“…In this way, amino acid transmitters are lost from the nerve terminal because of glial uptake, and, therefore, replenishment of the transmitter pool is required. Precursors for these amino acid transmitters could be synthesized in the nerve terminal and/or be transported into the terminal from astrocytes (Torgner & Kvamme, 1990). At present, the enzymatic equipment for the synthesis or metabolism of glutamate and GABA in amino-acidergic neurons and in astrocytes is attracting more attention Fonnum, 1984;Kugler, 1988bKugler, , 1989Torgner & Kvamme, 1990 1.…”

Section: Glutamate and Gaba As Neurotransmitters In The Hippocampusmentioning

confidence: 99%

“…1), more specifically involved in glutamate and GABA metabolism, are aspartate aminotransferase, glutamate dehydrogenase (GDH), glutamine synthetase, phosphate activated glutaminase, glutamate decarboxylase, and GABA transaminase (GABAT), which have been reviewed elsewhere (e.g. Fonnum, 1984;Torgner & Kvamme, 1990;Kugler, 1993). This paper focusses on NAD-ICDH, GDH and GABAT.…”

Section: Enzymes Related To the Amino Acid Transmitter Metabolismmentioning

confidence: 99%

In situ measurements of enzyme activities in the brain

Kügler

1993

Histochem J

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The present review focuses on enzymes involved in the metabolism of amino acid neurotransmitters and the microphotometric determinations of their activities in various layers of the rat hippocampus. The enzymes are NAD-linked isocitrate dehydrogenase (NAD-ICDH), glutamate dehydrogenase (GDH), and GABA transaminase (GABAT), all of which are localized in mitochondria. GDH seems to be restricted to astrocytes, whereas NAD-ICDH and GABAT are localized in neurons as well as in astrocytes. NAD-ICDH is an important enzyme of the tricarboxylic acid cycle and may deliver alpha-ketoglutarate for the formation of glutamate and GABA, which serve as neurotransmitters in the hippocampus. GDH catalyses the interconversion of alpha-ketoglutarate and glutamate, whereas GABAT is the important GABA-degrading enzyme and requires alpha-ketoglutarate for its activity. While differing in their cellular distribution and activity levels, NAD-ICDH, GDH and GABAT are significantly correlated in their hippocampal distribution. Furthermore, developmental and pharmacohistochemical studies suggest that the distribution and activity of astrocytic GDH is correlated with amino-acidergic neurotransmission in the hippocampus. The data reported give further evidence for a metabolic relationship between neurons and astrocytes in the turnover and metabolism of glutamate and GABA.

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Synthesis of transmitter glutamate and the glial-neuron interrelationship

Cited by 29 publications

References 29 publications

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Regulation of glial metabolism studied by ¹³C‐NMR

In situ measurements of enzyme activities in the brain

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Synthesis of transmitter glutamate and the glial-neuron interrelationship

Cited by 29 publications

References 29 publications

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

Regulation of glial metabolism studied by 13C‐NMR

In situ measurements of enzyme activities in the brain

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Regulation of glial metabolism studied by ¹³C‐NMR