The First in Vivo Observation of 13C–15N Coupling in Mammalian Brain

Kanamori, Keiko; Ross, Brian D.

doi:10.1006/jmre.2001.2432

Cited by 13 publications

(33 citation statements)

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“…Animal preparation and intravenous infusion Male Wistar rats (250 ± 10 g) were prepared for intravenous infusion through the femoral vein and allowed to recover for 24 h. This minimized the duration of anesthesia on the day of the NMR experiment and optimized physiological condition and brain glucose utilization under light anesthesia by intraperitoneal pentobarbital ($3.5 mg/kg weight every 15-20 min), as described previously (Kanamori and Ross 2001).…”

Section: Methodsmentioning

confidence: 99%

“…The probe (a surface 13 C-coil constructed by USA Instruments, Aurora, IN, USA), acquisition parameters for protondecoupled 13 C NMR and the method of quantitation of 13 C-metabolites have been described in detail previously (Kanamori and Ross 2001).…”

Section: Methodsmentioning

confidence: 99%

“…the feasibility of observing brain [5-13 C]GLU and [5-13 C, 15 N]GLN in vivo (Kanamori and Ross 2001); we now report quantitative time-course data (n ¼ 5-7) for flux determination. From the 13 C enrichment of extracellular GLU C5, the 15 N enrichments of the precursor ammonia and the rate of synthesis of [5-13 C, 15 N]GLN observed in vivo by NMR, the rate of glutamine synthesis derived from glial uptake of neurotransmitter GLU was determined.…”

mentioning

confidence: 96%

“…Our previous study showed that brain GLU can be 13 C enriched, predominantly at C5, by intravenous infusion of [2,[5][6][7][8][9][10][11][12][13] C]glucose (Kanamori and Ross 2001). The study also strongly suggested that the vesicular neurotransmitter GLU C5 can be selectively 13 C enriched by following the 2-h 13 C enrichment of whole-brain GLU C5 by chase with 12 C glucose.…”

mentioning

confidence: 99%

“…GLU and GLN concentrations ( 13 C + 12 C) in brain extracts were assayed by HPLC (Kanamori and Ross 2001). The concentrations of 13 C-and/or 15 N-enriched metabolites in brain extracts were measured by NMR as described previously (Kanamori and Ross 2001), except that a solenoidal 13 C probe (Advanced Imaging Research, Cleveland, OH, USA) was used for the in vitro measurement. For measurement of blood ammonia, serial arterial blood samples were taken in parallel bench-top infusion experiments.…”

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confidence: 99%

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Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Kanamori

Ross

Kondrat

2002

Journal of Neurochemistry

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Glial uptake of neurotransmitter glutamate (GLU) from the extracellular fluid was studied in vivo in rat brain by 13 C NMR and microdialysis combined with gas-chromatography/massspectrometry. Brain GLU C5 was 13 C enriched by intravenous [2,5-13 C]glucose infusion, followed by [ 12 C]glucose infusion to chase 13 C from the small glial GLU pool. This leaves [5-13 C]GLU mainly in the large neuronal metabolic pool and the vesicular neurotransmitter pool. During the chase, the 13 C enrichment of whole-brain GLU C5 was significantly lower than that of extracellular GLU (GLU ECF ) derived from exocytosis of vesicular GLU. Glial uptake of neurotransmitter N enrichment of precursor NH 3 (0.87 ± 0.014), the rate of synthesis of GLN (V¢ GLN ), derived from neurotransmitter GLU ECF , was determined to be 6.4 ± 0.44 lmol/g/h. Comparison with V GLN measured previously by an independent method showed that the neurotransmitter provides 80-90% of the substrate GLU pool for GLN synthesis. Hence, under our experimental conditions, the rate of 6.4 ± 0.44 lmol/g/h also represents a reasonable estimate for the rate of glial uptake of GLU ECF , a process that is crucial for protecting the brain from GLU excitotoxicity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Kanamori

Ross

Kondrat

2002

Journal of Neurochemistry

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Reduced glutamate neurotransmission in patients with Alzheimer's disease?an in vivo 13C magnetic resonance spectroscopy study

Lin

Shic²,

Enriquez³

et al. 2003

MAGMA Magnetic Resonance Materials in Physics, Biology and Medi

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Cognitive impairment in Alzheimer's disease (AD) is not fully explained. PET indicates reduced cerebral metabolic rate for glucose. Since glutamate neurotransmission (GNT) consumes more than 80% of the ATP generated from metabolism, a pilot study was carried out to determine the neuronal tricarboxylic acid cycle (TCA) based on the hypothesis that reduced GNT could contribute to cognitive impairment in AD. Three AD patients with cognitive impairment (mini-mental state exam: 24 vs 30, P<0.05) and significant reduction in both N-acetyl aspartate (NAA)/Creatine (Cr) ( P<0.009) and NAA/myo-inositol (mI) ratio ( P<0.01), and three age-matched controls each received 0.014-0.016 g/kg/min 99%1-13C glucose IV. Quantitative (1)H and proton-decoupled (13)C MR brain spectra were acquired from combined posterior-parietal white matter and posterior-cingulate gray matter every 5 min for 140 min.(13)C magnetic resonance spectroscopy (MRS) measures of glucose oxidation and neuronal TCA rate, including prolonged time to (13)C enrichment of glutamate (Glu2) ( P<0.004) and bicarbonate (HCO(3)) ( P<0.03) as well as reduced relative enrichment of Glu(2)/Glu(4) between 60 and 100 min ( P<0.04), were significantly different in AD patients vs. controls. (13)C measures of GNT, glutamine (Gln)(2)/Glu(2) ( P<0.02) and rates of glutamate enrichment (Glu(2)/glucose: 0.34 vs 0.86, P=ns and Glu(4)/glucose 0.26 vs 0.83, P=ns), were also reduced.(13)C MRS measures of neuronal TCA cycle, glucose oxidation and GNT were significantly correlated with measures of neuronal integrity: NAA/Cr, [NAA] and mI/NAA as determined by (1)H MRS ( R(2)=0.73-0.95; P<0.05-0.01), suggesting that impairment of GNT may be a contributing factor in the cognitive impairment characteristic of AD.

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Chronic electrographic seizure reduces glutamine and elevates glutamate in the extracellular fluid of rat brain

Kanamori

Ross

2011

Brain Research

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The First in Vivo Observation of 13C–15N Coupling in Mammalian Brain

Cited by 13 publications

References 30 publications

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Reduced glutamate neurotransmission in patients with Alzheimer's disease?an in vivo 13C magnetic resonance spectroscopy study

Chronic electrographic seizure reduces glutamine and elevates glutamate in the extracellular fluid of rat brain

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The First in Vivo Observation of 13C–15N Coupling in Mammalian Brain

Cited by 13 publications

References 30 publications

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and13C NMR

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and13C NMR

Reduced glutamate neurotransmission in patients with Alzheimer's disease?an in vivo 13C magnetic resonance spectroscopy study

Chronic electrographic seizure reduces glutamine and elevates glutamate in the extracellular fluid of rat brain

Contact Info

Product

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Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR