Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters

Hertz, Leif

doi:10.1016/0301-0082(79)90018-2

Cited by 607 publications

(304 citation statements)

References 299 publications

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“…This stands in contrast to the evidence that glutamate metabolism is compart mented into at least two kinetically (and morpho logically) distinct compartments with separate TCA cycles (for review see Hertz, 1979). The "small" glutamate pool, which is believed to be located in the astrocytes, is estimated to contain =11% (max- imally) of the total concentration of cerebral gluta mate (Cooper et aI., 1988).…”

Section: Discussionmentioning

confidence: 88%

“…therein). Glutamate metabolism occurs in at least two morphologically distinct cellular compartments (Hertz, 1979). A small, rapidly turning over pool of glutamate, thought to be the precursor of brain glu- 170 total glutamate concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Taking into account the 98-s time resolution and the sensitivity of the POCE experiment, we would not have detected the BC_ labeled fraction of glutamate that comprised a pool size less than =25% of the total concentration of cerebral glutamate or discerned glutamate turnover in a pool characterized by an exponential rate con stant faster than =0.33 min -I . Based on computer simulations of the kinetics of 14C labeling of amino acids and TCA cycle intermediates in the mouse brain from 14C-Iabeled glucose and acetate, Van den Berg and Garfinkel (1971) determined the flux to be = 1.25 j.1mol g -1 min -1 for the TCA cycle associ ated with the large glutamate pool (also see Hertz, 1979). Therefore, our results describing the turn over of the pool are compatible with estimated val ues of the rate of TCA cycle associated with the large (neuronal) pool of glutamate.…”

Section: Discussionmentioning

confidence: 99%

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The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy

Fitzpatrick

Hetherington

Behar

et al. 1990

J Cereb Blood Flow Metab

251

221

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Summary:The rate of incorporation of carbon from [1-13C]glucose into the and [3-CH21 of cerebral glutamate was measured in the rat brain in vivo by IH_ observed, 13C-edited (POCE) nuclear magnetic resonance (NMR) spectroscopy. Spectra were acquired every 98 s during a 6O-min infusion of [l-13C]glucose. Complete time courses were obtained from six animals. The measured intensity of the unresolved resonances of glu tamate and glutamine increased exponentially during the infusion and attained a steady state in -20 min with a first-order rate constant of 0. 130 ± 0.010 min -I (t1/2 = 5. 3 ± 0. 5 min). The appearance of the [3-13CH21 resonance in the POCE difference spectrum lagged behind that of the [4-13CH21 resonance and had not reached steady state at the end of the 60-min infusion (t1/2 = 26. 6 ± 4. 1 min). The increase observed in 13C-labeled glutamate represented isotopic enrichment and was not due to a change in the Cerebral glutamate functions as a neurotransmit ter, is necessary for cerebral ammonia detoxifica tion, and is directly related to cerebral energy me tabolism (see Cooper and Plum, 1987, and ref. therein). Glutamate metabolism occurs in at least two morphologically distinct cellular compartments (Hertz, 1979). A small, rapidly turning over pool of glutamate, thought to be the precursor of brain glu- 170 total glutamate concentration. The glucose infusion did not affect the levels of high-energy phosphates or intrac ellular pH as determined by 31p NMR spectroscopy. Since glucose carbon is incorporated into glutamate by rapid exchange with the tricarboxylic acid (TCA) cycle intermediate a-ketoglutarate, the rate of glutamate label ing provided an estimate of TCA cycle flux. We have determined the flux of carbon through the TCA cycle to be = 1.4 fLmol g -1 min -I. These experiments demon strate the feasibility of measuring metabolic fluxes in vivo using 13C-labeled glucose and the technique of 1 H observed, 13C-decoupled NMR spectroscopy. Key Words: Brain metabolism-[1-13C]Glucose-Glutamate Glycolysis-Nuclear magnetic resonance-Tricarboxylic acid cycle-Two-dimensional heteronuclear spectros copy.tamine, is located within the astrocytes. The pool of glutamate localized to the neurons is larger (at least 80% of total brain glutamate) and has a slower turn over rate than the astrocytic glutamate pool. Each glutamate pool is in equilibrium with a distinct tri carboxylic acid (TCA) cycle (Van den Berg et aI., 1969; Berl et aI., 1970). The flow of carbon from glucose to glutamate and the turnover time of the glutamate pool depend both on the rate of glycolysis and on the rate of entry of glucose carbon into the TCA cycle. Although turnover rates for glutamate have been estimated by radioactive tracer and sta ble isotope studies (Berl et aI., 1962(Berl et aI., , 1970 Cooper et aI., 1988) there has been no acceptable way to measure these rates in vivo.The turnover of cerebral glutamate and other me tabolites can be determined in vivo by monitoring the site-specific incorporation of l 3C using l 3C_ en...

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy

Fitzpatrick

Hetherington

Behar

et al. 1990

J Cereb Blood Flow Metab

251

221

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“…They are actively involved in uptake and degradation of the amino acid neurotransmitters, glutamate and GABA, are involved in shuttling energy metabolites to neurons and are also important for maintenance of the blood-retinal barrier [9][10][11]. Astrocytes are intricately linked with the vasculature and have processes within the nerve fibre and ganglion cell layers [12].…”

Section: Introductionmentioning

confidence: 99%

Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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Aims: Glutamate recycling is a major function of retinal Müller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. Methods: Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D-aspartate, into Müller cells. Results: There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D-aspartate immunoreactivity was significantly increased in Müller cells of diabetic rats compared to controls (p<0.001). The EC 50 was found to increase by 0.304 log units in diabetic Müller cells compared with controls, suggesting that glutamate uptake is twice as efficient. Conclusions: These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Müller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.

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“…Glutamate is, under physiological, conditions strictly compartmentalized in the brain. When re leased into the extracellular space, glutamate is rap idly taken up by an uptake mechanism in the glial cells (Hertz, 1979). Studies using intracerebral mi crodialysis during the opening of the BBB with 10 mg protamine sulfate, the dose used in the present Specific gravity 1.0480 study, have shown that glutamate, glycine, and as partate increase in the extracellular fluid 30-50 min after the BBB opening and remain increased for at least 2 hours, i.e., the time period studied so far.…”

Section: Frontal Cortexmentioning

confidence: 99%

Blockade of AMPA Receptors Reduces Brain Edema following Opening of the Blood—Brain Barrier

Westergren

Johansson

1993

J Cereb Blood Flow Metab

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The aim of our study was to evaluate whether blockade of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors could reduce brain edema in two experimental models of edema following opening of the blood–brain barrier (BBB). The brain specific gravity was determined 2 h after opening the BBB by a 30-s infusion of protamine sulfate (10 mg in 200 μl 0.9% NaCl) or arabinose (1.5 or 1.8 mol/L, 0.06 ml · s−1) into the right internal carotid artery. Cisternal CSF was withdrawn for albumin determination before the carotid infusion and before killing 2 h later. After infusion of protamine sulfate or arabinose, CSF albumin increased in all groups. The brain specific gravity was significantly lower in the right than in the left (control) frontal, parietal, and occipital cortex and striatum. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenxo( F)quinoxaline), an AMPA receptor antagonist, given intravenously 10 min after opening the BBB (5 mg/kg), significantly increased the specific gravity in the treated rats ( p < 0.01 for the difference from control rats) without reducing CSF albumin or albumin extravasation in the brain as evaluated with Evans blue. We hypothesize that intracerebral (glial?) AMPA receptors may play a role in brain edema following opening of the BBB.

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Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters

Cited by 607 publications

References 299 publications

The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy

The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy

Glutamate uptake in retinal glial cells during diabetes

Blockade of AMPA Receptors Reduces Brain Edema following Opening of the Blood—Brain Barrier

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Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters

Cited by 607 publications

References 299 publications

The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by 1-Observed, 13C-Edited NMR Spectroscopy

The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by 1-Observed, 13C-Edited NMR Spectroscopy

Glutamate uptake in retinal glial cells during diabetes

Blockade of AMPA Receptors Reduces Brain Edema following Opening of the Blood—Brain Barrier

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The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy

The Flux from Glucose to Glutamate in the Rat Brain in vivo as Determined by ¹-Observed, ¹³C-Edited NMR Spectroscopy