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13C NMR Spectroscopy as a Tool in Neurobiology

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Neural Metabolism In Vivo

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 4))

Abstract

Studies of the complex interactions in intermediary metabolism between neurons and glia in cell cultures and animal models are important in order to understand normal physiology, and the origin and development of psychiatric and neurological diseases in humans. This chapter will give examples of how cell culture studies using glutamatergic neurons from cerebellum, GABAergic neurons from cerebral cortex and astrocytes from both areas can be used to probe the importance of the tricarboxylic acid cycle, transamination reactions and glutamine synthesis. The middle cerebral artery occlusion model of ischemic stroke, the pentylene tetrazole model of epileptic seizures, the pilocarpine and kainic acid models of mesial temporal lobe epilepsy in rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS), will be used to describe what 13C nuclear magnetic resonance spectroscopy analysis of rat brain extracts can tell us about metabolism in the diseased brain.

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References

  • Alves PM, Flogel U, Brand A, Leibfritz D, Carrondo MJ, Santos H, Sonnewald U (1996) Immobilization of primary astrocytes and neurons for online monitoring of biochemical processes by NMR. Dev Neurosci 18:478–483

    Article  PubMed  CAS  Google Scholar 

  • Alves PM, Nunes R, Zhang C, Maycock CD, Sonnewald U, Carrondo MJ, Santos H (2000) Metabolism of 3-13C-malate in primary cultures of mouse astrocytes. Dev Neurosci 22:456–462

    Article  PubMed  CAS  Google Scholar 

  • Alvestad S, Hammer J, Eyjolfsson E, Qu H, Ottersen OP, Sonnewald U (2008) Limbic structures show altered glial-neuronal metabolism in the chronic phase of kainate induced epilepsy. Neurochem Res 33:257–266

    Article  PubMed  CAS  Google Scholar 

  • Alvestad S, Hammer J, Qu H, Håberg A, Ottersen OP, Sonnewald U (2011) Reduced astrocytic contribution to the turnover of glutamate, glutamine, and GABA characterizes the latent phase in the kainate model of temporal lobe epilepsy. JCBFM 31(8):1675–1686

    Google Scholar 

  • Bachelard H (1998) Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of neuronal/glial relationships. Dev Neurosci 20:277–288

    Article  PubMed  CAS  Google Scholar 

  • Badar-Goffer RS, Bachelard HS, Morris PG (1990) Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem J 266:133–139

    PubMed  CAS  Google Scholar 

  • Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS (2006) Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab 26:1285–1297

    Article  PubMed  CAS  Google Scholar 

  • Bak LK, Waagepetersen HS, Melø TM, Schousboe A, Sonnewald U (2007) Complex glutamate labeling from [U-13C]glucose or [U-13C]lactate in co-cultures of cerebellar neurons and astrocytes. Neurochem Res 32:671–680

    Article  PubMed  CAS  Google Scholar 

  • Bakken IJ, Johnsen SF, White LR, Unsgard G, Aasly J, Sonnewald U (1997) NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes. J Neurosci Res 47:642–649

    Article  PubMed  CAS  Google Scholar 

  • Barany M, Arus C, Chang YC (1985) Natural-abundance 13C NMR of brain. Magn Reson Med 2:289–295

    Article  PubMed  CAS  Google Scholar 

  • Baxter CF, Roberts E (1961) Elevation of gamma-aminobutyric acid in brain: selective inhibition of gamma-aminobutyric-alpha-ketoglutaric acid transaminase. J Biol Chem 236:3287–3294

    PubMed  CAS  Google Scholar 

  • Beckmann N, Turkalj I, Seelig J, Keller U (1991) 13C NMR for the assessment of human brain glucose metabolism in vivo. Biochemistry 30:6362–6366

    Article  PubMed  CAS  Google Scholar 

  • Benjamin AM (1981) Control of glutaminase activity in rat brain cortex in vitro: influence of ­glutamate, phosphate, ammonium, calcium and hydrogen ions. Brain Res 208:363–377

    Article  PubMed  CAS  Google Scholar 

  • Blüml S, Moreno A, Hwang JH, Ross BD (2001) 1-13C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders. NMR Biomed 14:19–32

    Article  PubMed  Google Scholar 

  • Blüml S, Moreno-Torres A, Shic F, Nguy CH, Ross BD (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed 15:1–5

    Article  PubMed  CAS  Google Scholar 

  • Bradford HF (1995) Glutamate, GABA and epilepsy. Prog Neurobiol 47:477–511

    Article  PubMed  CAS  Google Scholar 

  • Castillo J, Davalos A, Naveiro J, Noya M (1996) Neuroexcitatory amino acids and their relation to infarct size and neurological deficit in ischemic stroke. Stroke 27:1060–1065

    Article  PubMed  CAS  Google Scholar 

  • Cerdan S, Kunnecke B, Seelig J (1990) Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR. J Biol Chem 265:12916–12926

    PubMed  CAS  Google Scholar 

  • Cerdán S, Rodrigues TB, Sierra A, Benito M, Fonseca LL, Fonseca CP, García-Martín ML (2006) The redox switch/redox coupling hypothesis. Neurochem Int 48:523–530

    Article  PubMed  CAS  Google Scholar 

  • Choi DW (1994) Glutamate receptors and the induction of excitotoxic neuronal death. Prog Brain Res 100:47–51

    Article  PubMed  CAS  Google Scholar 

  • Choi IY, Gruetter R (2003) In vivo 13C NMR assessment of brain glycogen concentration and turnover in the awake rat. Neurochem Int 43:317–322

    Article  PubMed  CAS  Google Scholar 

  • Cremer JE, Lucas HM (1971) Sodium pentobarbitone and metabolic compartments in rat brain. Brain Res 35:619–621

    Article  PubMed  CAS  Google Scholar 

  • de Lanerolle NC, Lee TS (2005) New facets of the neuropathology and molecular profile of human temporal lobe epilepsy. Epilepsy Behav 10:190–203

    Article  Google Scholar 

  • Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37

    Article  PubMed  CAS  Google Scholar 

  • Eloqayli H, Dahl CB, Gotestam KG, Unsgard G, Hadidi H, Sonnewald U (2003) Pentylenetetrazole decreases metabolic glutamate turnover in rat brain. J Neurochem 85:1200–1207

    Article  PubMed  CAS  Google Scholar 

  • Erecinska M, Nelson D, Daikhin Y, Yudkoff M (1996) Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium, and ketone bodies. J Neurochem 67:2325–2334

    Article  PubMed  CAS  Google Scholar 

  • Fan TWM (1996) Metabolite profiling by one and two-dimensional NMR analysis of complex mixture. Prog Nucl Magn Reson Spectrosc 528:161–219

    Google Scholar 

  • Fan TW-M, Lane AN (2008) Structure-based profiling of metabolites and isotopomers by NMR. Prog Nucl Magn Reson Spectrosc 52:69–117

    Article  CAS  Google Scholar 

  • Freo U, Ori C (2004) Effects of anesthesia and recovery from ketamine racemate and enantiomers on regional cerebral glucose metabolism in rats. Anesthesiology 100:1172–1178

    Article  PubMed  CAS  Google Scholar 

  • Fujibayashi Y, Waki A, Wada K, Ueno M, Magata Y, Yonekura Y, Konishi J, Takeda T, Yokoyama A (1994) Differential aging pattern of cerebral accumulation of radiolabeled glucose and amino acid in the senescence accelerated mouse (SAM), a new model for the study of memory impairment. Biol Pharm Bull 17:102–105

    Article  PubMed  CAS  Google Scholar 

  • Gaitonde MK, Dahl DR, ElliotT KA (1965) Entry of glucose carbon into amino acids of rat brain and liver in vivo after injection of uniformly 14-C-labelled glucose. Biochem J 94:345–352

    PubMed  CAS  Google Scholar 

  • Garcia-Espinosa MA, Rodrigues TB, Sierra A, Benito M, Fonseca C, Gray HL, Bartnik BL, Garcia-Martin ML, Ballesteros P, Cerdan S (2004) Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy. Neurochem Int 45:297–303

    Article  PubMed  CAS  Google Scholar 

  • Gibson GE, Sheu KF, Blass JP (1998) Abnormalities of mitochondrial enzymes in Alzheimer ­disease. J Neural Transm 105:855–870

    Article  PubMed  CAS  Google Scholar 

  • Griffin JL, Rae C, Radda GK, Matthews PM (1999) Delayed labelling of brain glutamate after an intra-arterial [13C]glucose bolus: evidence for aerobic metabolism of guinea pig brain glycogen store. Biochim Biophys Acta 1450:297–307

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Novotny EJ, Boulware SD, Rothman DL, Mason GF, Shulman GI, Shulman RG, Tamborlane WV (1992) Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. Proc Natl Acad Sci USA 89:1109–1112. Erratum in: Proc Natl Acad Sci USA 1992 Dec 15;89(24):12208

    Google Scholar 

  • Haberg A, Qu H, Bakken IJ, Sande LM, White LR, Haraldseth O, Unsgard G, Aasly J, Sonnewald U (1998a) In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain. Dev Neurosci 20:389–398

    Article  PubMed  CAS  Google Scholar 

  • Haberg A, Qu H, Haraldseth O, Unsgard G, Sonnewald U (1998b) In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 18:1223–1232

    Article  PubMed  CAS  Google Scholar 

  • Haberg A, Qu H, Saether O, Unsgard G, Haraldseth O, Sonnewald U (2001) Differences in neurotransmitter synthesis and intermediary metabolism between glutamatergic and GABAergic neurons during 4 hours of middle cerebral artery occlusion in the rat: the role of astrocytes in neuronal survival. J Cereb Blood Flow Metab 21:1451–1463

    Article  PubMed  CAS  Google Scholar 

  • Haberg A, Qu H, Hjelstuen MH, Sonnewald U (2006) Glutamate and GABA metabolism in transient and permanent middle cerebral artery occlusion in rat: importance of astrocytes for neuronal survival. Neurochem Int 48:531–540

    Article  PubMed  CAS  Google Scholar 

  • Haberg A, Qu H, Hjelstuen MH, Sonnewald U (2007) Effect of the pyrrolopyrimidine lipid peroxidation inhibitor U-101033E on neuronal and astrocytic metabolism and infarct volume in rats with transient middle cerebral artery occlusion. Neurochem Int 50:932–940

    Article  PubMed  CAS  Google Scholar 

  • Haberg AK, Qu H, Sonnewald U (2009) Acute changes in intermediary metabolism in cerebellum and contralateral hemisphere following middle cerebral artery occlusion in rat. J Neurochem 109(Suppl 1):174–181

    Article  PubMed  CAS  Google Scholar 

  • Hansen TD, Warner DS, Todd MM, Vust LJ, Trawick DC (1988) Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats. Anesthesiology 69:332–337

    Article  PubMed  CAS  Google Scholar 

  • Harada M, Okuda C, Sawa T, Murakami T (1992) Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose- and saline-infused rats. Anesthesiology 77:728–734

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Sonnewald U (1995a) Selective inhibition of the tricarboxylic acid cycle of GABAergic neurons with 3-nitropropionic acid in vivo. J Neurochem 65:1184–1191

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Sonnewald U (1995b) Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids? J Neurochem 65:2227–2234

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Sonnewald U, Fonnum F (1995) Glial-neuronal interactions as studied by cerebral metabolism of [2-13C]acetate and [1-13C]glucose: an ex vivo 13C NMR spectroscopic study. J Neurochem 64:2773–2782

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Bachelard H, Jones P, Fonnum F, Sonnewald U (1997) Trafficking of amino acids between neurons and glia in vivo. Effects of inhibition of glial metabolism by fluoroacetate. J Cereb Blood Flow Metab 17:1230–1238

    Article  PubMed  CAS  Google Scholar 

  • Henry PG, Tkac I, Gruetter R (2003) 1H-localized broadband 13C NMR spectroscopy of the rat brain in vivo at 9.4 T. Magn Reson Med 50:684–692

    Article  PubMed  CAS  Google Scholar 

  • Henry PG, Adriany G, Deelchand D, Gruetter R, Marjanska M, Oz G, Seaquist ER, Shestov A, Ug˘urbil K (2006) In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective. Magn Reson Imaging 24:527–539

    Article  PubMed  CAS  Google Scholar 

  • Hertz E, Yu ACH, Shahar A, Juurlink BHJ, Schousboe A (1989a) Preparation of primary cultures of mouse cortical neurons. In: A dissection and tissue culture manual for the nervous system. Alan R. Liss, New York, pp 183–186

    Google Scholar 

  • Hertz L, Juurlink BHJ, Hertz E, Fosmark H, Schousboe A (1989b) Preparation of primary cultures of mouse (rat) astrocytes. In: A dissection and tissue culture manual for the nervous system. Alan R. Liss, New York, pp 105–108

    Google Scholar 

  • Hoffman WE, Edelman G, Kochs E, Werner C, Segil L, Albrecht RF (1991) Cerebral autoregulation in awake versus isoflurane-anesthetized rats. Anesth Analg 73:753–757

    PubMed  CAS  Google Scholar 

  • Hogstad S, Svenneby G, Torgner IA, Kvamme E, Hertz L, Schousboe A (1988) Glutaminase in neurons and astrocytes cultured from mouse brain: kinetic properties and effects of phosphate, glutamate, and ammonia. Neurochem Res 13:383–388

    Article  PubMed  CAS  Google Scholar 

  • Hosford DA (1995) Models of primary generalized epilepsy. Curr Opin Neurol 8:121–125

    Article  PubMed  CAS  Google Scholar 

  • Hyder F, Brown P, Nixon TW, Behar KL (2003) Mapping cerebral glutamate 13C turnover and oxygen consumption by in vivo NMR. Adv Exp Med Biol 530:29–39

    Article  PubMed  CAS  Google Scholar 

  • Karelson G, Ziegler A, Kunnecke B, Seelig J (2003) Feeding versus infusion: a novel approach to study the NAA metabolism in rat brain. NMR Biomed 16:413–423

    Article  PubMed  CAS  Google Scholar 

  • Kauppinen RA, Pirttilä TR, Auriola SO, Williams SR (1994) Compartmentation of cerebral glutamate in situ as detected by 1H/13C n.m.r. Biochem J 298:121–127

    PubMed  CAS  Google Scholar 

  • Kondziella D, Bidar A, Urfjell B, Sletvold O, Sonnewald U (2002) The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and metabolism. Neurochem Int 40:413–418

    Article  PubMed  CAS  Google Scholar 

  • Kondziella D, Hammer J, Sletvold O, Sonnewald U (2003) The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: glial-neuronal metabolic interactions. Neurochem Int 43:629–637

    Article  PubMed  CAS  Google Scholar 

  • Kvamme E, Roberg B, Torgner IA (2000) Phosphate-activated glutaminase and mitochondrial glutamine transport in the brain. Neurochem Res 25:1407–1419

    Article  PubMed  CAS  Google Scholar 

  • Laake JH, Slyngstad TA, Haug FM, Ottersen OP (1995) Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: immunogold evidence from hippocampal slice cultures. J Neurochem 65:871–881

    Article  PubMed  CAS  Google Scholar 

  • Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci 22:1523–1531

    PubMed  CAS  Google Scholar 

  • Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    Article  PubMed  CAS  Google Scholar 

  • Magistretti PJ, Pellerin L, Rothman DL, Shulman RG (1999) Energy on demand. Science 283:496–497

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ (1995) Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab 15:12–25

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL (2007) Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem 100:73–86

    Article  PubMed  CAS  Google Scholar 

  • McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR (1996) Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66: 386–393

    Article  PubMed  CAS  Google Scholar 

  • McKenna MC, Dienel GA, Sonnewald U, Waagepetersen HS, Schousboe A (2011) Energy metabolism of the brain. In: Siegel G, Albers W, Brady S, Price D (eds) Basic neurochemistry, vol 8, Elsevier, London, pp 201–226, ISBN 978-0-12-374947-5

    Google Scholar 

  • Melø TM, Nehlig A, Sonnewald U (2005) Metabolism is normal in astrocytes in chronically epileptic rats: a 13C NMR study of neuronal-glial interactions in a model of temporal lobe epilepsy. J Cereb Blood Flow Metab 25:1254–1264

    Article  PubMed  CAS  Google Scholar 

  • Melø TM, Bastholm IA, Sonnewald U, Nehlig A (2007) Astrocytes may play a role in the etiology of absence epilepsy: a comparison between immature GAERS not yet expressing seizures and adults. Neurobiol Dis 28:227–235

    Article  PubMed  CAS  Google Scholar 

  • Memezawa H, Minamisawa H, Smith ML, Siesjo BK (1992) Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat. Exp Brain Res 89:67–78

    Article  PubMed  CAS  Google Scholar 

  • Minchin MC, Beart PM (1975a) Compartmentation of amino acid metabolism in the rat dorsal root ganglion; a metabolic and autoradiographic study. Brain Res 83:437–449

    Article  PubMed  CAS  Google Scholar 

  • Minchin MC, Beart PM (1975b) Compartmentation of amino acid metabolism in the rat posterior pituitary. J Neurochem 24:881–884

    Article  PubMed  CAS  Google Scholar 

  • Moreno A, Blüml S, Hwang JH, Ross BD (2001a) Alternative 1-13C glucose infusion protocols for clinical 13C MRS examinations of the brain. Magn Reson Med 46:39–48

    Article  PubMed  CAS  Google Scholar 

  • Moreno A, Ross BD, Blüml S (2001b) Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by 13C MRS and [1-13C]glucose infusion. J Neurochem 771:347–350

    Article  Google Scholar 

  • Muller TB, Haraldseth O, Jones RA, Sebastiani G, Godtliebsen F, Lindboe CF, Unsgard G (1995) Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. Stroke 26:451–457

    Article  PubMed  CAS  Google Scholar 

  • Muller B, Qu H, Garseth M, White LR, Aasly J, Sonnewald U (2000) Amino acid neurotransmitter metabolism in neurones and glia following kainate injection in rats. Neurosci Lett 279:169–172

    Article  PubMed  CAS  Google Scholar 

  • Nehlig A, Wittendorp-Rechenmann E, Lam CD (2004) Selective uptake of [14  C]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14  C-trajectography combined with immunohistochemistry. J Cereb Blood Flow Metab 24:1004–1014

    Article  PubMed  CAS  Google Scholar 

  • Obrenovitch TP (1996) Origins of glutamate release in ischaemia. Acta Neurochir Suppl 66:50–55

    PubMed  CAS  Google Scholar 

  • Olstad O, Qu H, Sonnewald U (2007) Glutamate is preferred over glutamine for intermediary metabolism in cultured cerebellar neurons. J Cereb Blood Flow Metab 50:1004–1013

    CAS  Google Scholar 

  • Ottersen OP, Storm-Mathisen J (1984) Glutamate- and GABA-containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique. J Comp Neurol 229:374–392

    Article  PubMed  CAS  Google Scholar 

  • Oz G, Berkich DA, Henry PG, Xu Y, LaNoue K, Hutson SM, Gruetter R (2004) Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci 24:11273–11279

    Article  PubMed  CAS  Google Scholar 

  • Oz G, Seaquist ER, Kumar A, Criego AB, Benedict LE, Rao JP, Henry PG, Van De Moortele PF, Gruetter R (2007) Human brain glycogen content and metabolism: implications on its role in brain energy metabolism. Am..J Physiol. Endocrinol Metab 292:E946–51

    CAS  Google Scholar 

  • Pan JW, de Graaf RA, Petersen KF, Shulman GI, Hetherington HP, Rothman DL (2002) [2,4-13C2 ]-beta-Hydroxybutyrate metabolism in human brain. J Cereb Blood Flow Metab 22:890–898

    Article  PubMed  CAS  Google Scholar 

  • Pascual JM, Carceller F, Roda JM, Cerdán S (1998) Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats. Stroke 29:1048–1056, discussion 1056–1057

    Article  PubMed  CAS  Google Scholar 

  • Pellerin L, Bouzier-Sor AK, Aubert A, Serres S, Merle M, Costala R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262

    Article  PubMed  Google Scholar 

  • Peng L, Zhang X, Hertz L (1994) High extracellular potassium concentrations stimulate oxidative metabolism in a glutamatergic neuronal culture and glycolysis in cultured astrocytes but have no stimulatory effect in a GABAergic neuronal culture. Brain Res 663:168–172

    Article  PubMed  CAS  Google Scholar 

  • Petroff OA, Errante LD, Rothman DL, Kim JH, Spencer DD (2002) Glutamate-glutamine cycling in the epileptic human hippocampus. Epilepsia 43:703–710

    Article  PubMed  CAS  Google Scholar 

  • Qu H, Haberg A, Haraldseth O, Unsgard G, Sonnewald U (2000a) 13C MR spectroscopy study of lactate as substrate for rat brain. Dev Neurosci 22:429–436

    Article  PubMed  CAS  Google Scholar 

  • Qu H, Waagepetersen HS, van Hengel M, Wolt S, Dale O, Unsgard G, Sletvold O, Schousboe A, Sonnewald U (2000b) Effects of thiopental on transport and metabolism of glutamate in cultured cerebellar granule neurons. Neurochem Int 37:207–215

    Article  PubMed  CAS  Google Scholar 

  • Qu H, Konradsen JR, van HM, Wolt S, Sonnewald U (2001a) Effect of glutamine and GABA on [U-13C]glutamate metabolism in cerebellar astrocytes and granule neurons. J Neurosci Res 66:885–890

    Article  PubMed  CAS  Google Scholar 

  • Qu H, van der GM, Le MT, Sonnewald U (2001b) The effect of thiopental on glutamate metabolism in mouse cerebellar astrocytes in vitro. Neurosci Lett 304:141–144

    Google Scholar 

  • Qu H, Eloqayli H, Müller B, Aasly J, Sonnewald U (2003) Glial-neuronal interactions following kainate injection in rats. Neurochem Int 42:101–106

    Google Scholar 

  • Rae C, Moussa Cel-H, Griffin JL, Parekh SB, Bubb WA, Hunt NH, Balcar VJA (2006) Metabolomic approach to ionotropic glutamate receptor subtype function: a nuclear magnetic resonance in vitro investigation. J Cereb Blood Flow Metab 26:1005–1017

    Article  PubMed  CAS  Google Scholar 

  • Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10:1377–1386

    Article  PubMed  CAS  Google Scholar 

  • Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic–ischemic brain damage. Ann Neurol 19:105–111

    Article  PubMed  CAS  Google Scholar 

  • Rothman DL, Howseman AM, Graham GD, Petroff OA, Lantos G, Fayad PB, Brass LM, Shulman GI, Shulman RG, Prichard JW (1991) Localized proton NMR observation of [3-13C]lactate in stroke after [1-13C]glucose infusion. Magn Reson Med 21:302–307

    Article  PubMed  CAS  Google Scholar 

  • Rothman DL, Novotny EJ, Shulman GI, Howseman AM, Petroff OA, Mason G, Nixon T, Hanstock CC, Prichard JW, Shulman RG (1992) 1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain. Proc Natl Acad Sci USA 89:9603–9606

    Article  PubMed  CAS  Google Scholar 

  • Sato E, Inoue A, Kurokawa T, Ishibashi S (1994) Early changes in glucose metabolism in the cerebrum of senescence accelerated mouse: involvement of glucose transporter. Brain Res 637:133–138

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A, Wu JY, Roberts E (1973) Purification and characterization of the 4-aminobutyrate–2, ketoglutarate transaminase from mouse brain. Biochemistry 12:2868–2873

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A, Meier E, Drejer J, Hertz L (1989) Preparation of primary cultures of mouse (rat) cerebellar granule cells. In: A dissection and tissue culture manual for the nervous system. Alan R. Liss, New York, pp 183–186

    Google Scholar 

  • Schroeder H, Becker A, Schroeder U, Hoellt V (1999) 3  H-L-glutamate binding and 3 H-D-aspartate release from hippocampal tissue during the development of pentylenetetrazole kindling in rats. Pharmacol Biochem Behav 62:349–352

    Article  PubMed  CAS  Google Scholar 

  • Schwartz-Bloom RD, Sah R (2001) gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 77:353–371

    Article  PubMed  CAS  Google Scholar 

  • Serres S, Bouyer JJ, Bezancon E, Canioni P, Merle M (2003) Involvement of brain lactate in neuronal metabolism. NMR Biomed 16:430–439

    Article  PubMed  CAS  Google Scholar 

  • Serres S, Bezancon E, Franconi JM, Merle M (2004) Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity. J Biol Chem 279:47881–47889

    Article  PubMed  CAS  Google Scholar 

  • Shank RP, Leo GC, Zielke HR (1993) Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J Neurochem 61:315–323

    Article  PubMed  CAS  Google Scholar 

  • Shic F, Ross B (2003) Automated data processing of [1H-decoupled] 13C MR spectra acquired from human brain in vivo. J Magn Reson 162:259–268

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG (1997) In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci USA 94:2699–2704

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Mason GF, Shen J, Cline GW, Herskovits AZ, Wall JE, Behar KL, Rothman DL, Shulman RG (2001) In vivo 13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J Neurochem 2001(76):975–989

    Google Scholar 

  • Sommer W (1880) Erkrankung des Ammonshorns als aetiologisches Moment der Epilepsie. Arch Psychiatr Nervenkr 10:631–675

    Article  Google Scholar 

  • Sonnewald U, Rae C (2010) Pyruvate carboxylation in different model systems studied by 13C MRS. Neurochem Res 35(12):1916–21

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Westergaard N, Krane J, Unsgard G, Petersen SB, Schousboe A (1991) First direct demonstration of preferential release of citrate from astrocytes using [13C]NMR spectroscopy of cultured neurons and astrocytes. Neurosci Lett 128:235–239

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Petersen SB, Krane J, Westergaard N, Schousboe A (1992) 1H NMR study of cortex neurons and cerebellar granule cells on microcarriers and their PCA extracts: lactate production under hypoxia. Magn Reson Med 23:166–171

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Westergaard N, Petersen SB, Unsgard G, Schousboe A (1993a) Metabolism of [U-13C]glutamate in astrocytes studied by 13C NMR spectroscopy: incorporation of more label into lactate than into glutamine demonstrates the importance of the tricarboxylic acid cycle. J Neurochem 61:1179–1182

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Westergaard N, Schousboe A, Svendsen JS, Unsgard G, Petersen SB (1993b) Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem Int 22:19–29

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, White LR, Odegard E, Westergaard N, Bakken IJ, Aasly J, Unsgard G, Schousboe A (1996) MRS study of glutamate metabolism in cultured neurons/glia. Neurochem Res 21:987–993

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Olstad E, Qu H, Babot Z, Cristofòfol R, Suñol C, Schousboe A, Waagepetersen H (2004) First direct demonstration of extensive GABA synthesis in mouse cerebellar neuronal cultures. J Neurochem 91:796–803

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Schousboe A, Waagepetersen HW (2011) 13C NMR spectroscopy and mass ­spectrometry analysis of intermediary metabolism in cultured neural cells in Neuromethods. W Walz (Series ed), Aschner M (Volume Eds), Sunol C, Price A. Springer Science-Business Media, New York, pp 403–414, ISBN 978-1-61779-076-8, http://issuu.com/asartehutiimhotep/docs/cell-culturing-techniques

  • Stephen LJ, Brodie MJ (2000) Epilepsy in elderly people. Lancet 355:1441–1446

    Article  PubMed  CAS  Google Scholar 

  • Swanson RA, Shiraishi K, Morton MT, Sharp FR (1990) Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion. Stroke 21:322–327

    Article  PubMed  CAS  Google Scholar 

  • Sze PY (1979) L-Glutamate decarboxylase. Adv Exp Med Biol 123:59–78

    PubMed  CAS  Google Scholar 

  • Takagi K, Ginsberg MD, Globus MY, Dietrich WD, Martinez E, Kraydieh S, Busto R (1993) Changes in amino acid neurotransmitters and cerebral blood flow in the ischemic penumbral region following middle cerebral artery occlusion in the rat: correlation with histopathology. J Cereb Blood Flow Metab 13:575–585

    Article  PubMed  CAS  Google Scholar 

  • Taylor A, McLean M, Morris P, Bachelard H (1996) Approaches to studies on neuronal/glial relationships by 13C-MRS analysis. Dev Neurosci 18:434–442

    Article  PubMed  CAS  Google Scholar 

  • Tirilazad International Steering Committee (2000) Tirilazad mesylate in acute ischemic stroke: A systematic review. Stroke 31:2257–2265

    Article  PubMed  CAS  Google Scholar 

  • Torp R, Arvin B, Le PE, Chapman AG, Ottersen OP, Meldrum BS (1993) Effect of ischaemia and reperfusion on the extra- and intracellular distribution of glutamate, glutamine, aspartate and GABA in the rat hippocampus, with a note on the effect of the sodium channel blocker BW1003C87. Exp Brain Res 96:365–376

    Article  PubMed  CAS  Google Scholar 

  • Tyson RL, Gallagher C, Sutherland GR (2003) 13C-Labeled substrates and the cerebral metabolic compartmentalization of acetate and lactate. Brain Res 992:43–52

    Article  PubMed  CAS  Google Scholar 

  • Vrba R (1962) Glucose metabolism in rat brain in vivo. Nature 195:663–665

    Article  PubMed  CAS  Google Scholar 

  • Waagepetersen HS, Bakken IJ, Larsson OM, Sonnewald U, Schousboe A (1998) Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy. J Cereb Blood Flow Metab 18:109–117

    Article  PubMed  CAS  Google Scholar 

  • Waagepetersen HS, Qu H, Schousboe A, Sonnewald U (2001) Elucidation of the quantitative significance of pyruvate carboxylation in cultured cerebellar neurons and astrocytes. J Neurosci Res 66:763–770

    Article  PubMed  CAS  Google Scholar 

  • Waagepetersen H, Melø T, Schousboe A, Sonnewald U (2004) Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical neurons is influenced by environmental cues. J Neurosci Res (in press)

    Google Scholar 

  • Waagepetersen HS, Qu H, Sonnewald U, Shimamoto K, Schousboe A (2005a) Role of glutamine and neuronal glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic neurons. Neurochem Int 47:92–102

    Article  PubMed  CAS  Google Scholar 

  • Waagepetersen HS, Melø TM, Schousboe A, Sonnewald U (2005b) Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical neurons is influenced by environmental cues. J Neurosci Res 79:97–105

    Article  PubMed  CAS  Google Scholar 

  • Waagepetersen HS, Qu H, Sonnewald U, Schousboe A (2009) Energy and amino acid neurotransmitter metabolism in astrocytes. In: Parpura V, Haydon PG, (eds), Astrocytes in (patho)physiology of the nervous system, Springer, Boston, pp 177–200

    Google Scholar 

  • Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225–5233

    PubMed  CAS  Google Scholar 

  • Westergaard N, Fosmark H, Schousboe A (1991a) Metabolism and release of glutamate in cerebellar granule cells cocultured with astrocytes from cerebellum or cerebral cortex. J Neurochem 56:59–66

    Article  PubMed  CAS  Google Scholar 

  • Westergaard N, Sonnewald U, Petersen SB, Schousboe A (1991b) Characterization of microcarrier cultures of neurons and astrocytes from cerebral cortex and cerebellum. Neurochem Res 16:919–923

    Article  PubMed  CAS  Google Scholar 

  • Westergaard N, Larsson OM, Jensen B, Schousboe A (1992) Synthesis and release of GABA in cerebral cortical neurons co-cultured with astrocytes from cerebral cortex or cerebellum. Neurochem Int 20:567–575

    Article  PubMed  CAS  Google Scholar 

  • Westergaard N, Drejer J, Schousboe A, Sonnewald U (1996) Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C]glutamate. Glia 17:160–168

    Article  PubMed  CAS  Google Scholar 

  • Whitehead KJ, Rose S, Jenner P (2004) Halothane anesthesia affects NMDA-stimulated cholinergic and GABAergic modulation of striatal dopamine efflux and metabolism in the rat in vivo. Neurochem Res 29:835–842

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neuroscience, Norwegian University of Science & Technology, Trondheim, Norway

    Asta Haberg M.D., Ph.D., Ursula Sonnewald Ph.D., Janniche Hammer Ph.D. & Torun Melø Ph.D.

  2. Department of Neuroscience, Jordan University of Science and Technology (JUST), Irbid, Jordan

    Haytham Eloqayli

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  1. Asta Haberg M.D., Ph.D.
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  2. Ursula Sonnewald Ph.D.
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  3. Janniche Hammer Ph.D.
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  4. Torun Melø Ph.D.
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  5. Haytham Eloqayli
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Correspondence to Ursula Sonnewald Ph.D. .

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Editors and Affiliations

  1. School of Medicine, Hoglund Brain Imaging Center, University of Kansas, Rainbow Blvd. 3901, Kansas City, 66160, Kansas, USA

    In-Young Choi

  2. Inst. Physique de la Matière Complexe, Labo. d'Imagerie Fonctionnelle et, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland

    Rolf Gruetter

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Haberg, A., Sonnewald, U., Hammer, J., Melø, T., Eloqayli, H. (2012). 13C NMR Spectroscopy as a Tool in Neurobiology. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_8

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