Skip to main content
SpringerLink
Log in

NMR Spectroscopy of Brain Glutamate Function

  • Protocol
  • First Online:
Biochemical Approaches for Glutamatergic Neurotransmission

Part of the book series: Neuromethods ((NM,volume 130))

  • 1167 Accesses

Abstract

Glutamate has fundamentally important functions in the CNS. It is the principal excitatory neurotransmitter as well as a key metabolite linking carbon and nitrogen metabolism. The dual roles of glutamate as a neurotransmitter and metabolite are intricately connected. Its unusually high concentration and rapid turnover in brain make it accessible to both proton and 13C NMR spectroscopy methods. This has enabled researchers to study the various functions of glutamate in basic neuroscience and brain disorders noninvasively and in vivo. Here, we provide an overview of proton and heteronuclear nuclear magnetic resonance (NMR) spectroscopy techniques and their applications to studying glutamate metabolism and glutamatergic neurotransmission in brain with emphasis placed on recent progress.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Erecinska M, Silver IA (1990) Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 35:245–296

    Article  CAS  PubMed  Google Scholar 

  2. Gunther H (1992) NMR spectroscopy, basic principles, concepts, and applications in chemistry, 2nd edn. John Wiley & Sons, New York

    Google Scholar 

  3. Braun S, Kalinowski HO, Berger S (1998) 150 and more basic NMR experiments, a practical guide, 2nd edn. Wiley-VCH, Weinheim

    Google Scholar 

  4. Slichter CP (1996) Principles of magnetic resonance, 3rd edn. Springer, Berlin

    Google Scholar 

  5. Derome AE (1987) Modern NMR techniques for chemistry research. Pergamon Press, Oxford

    Google Scholar 

  6. Siesjö BK (1978) Brain energy metabolism. John Wiley & Sons, Chichester, UK

    Google Scholar 

  7. Ende G (2015) Proton magnetic resonance spectroscopy: relevance of glutamate and GABA to neuropsychology. Neuropsychol Rev 25(3):315–325

    Article  PubMed  Google Scholar 

  8. Gigante AD, Bond DJ, Lafer B et al (2012) Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 14(5):478–487

    Article  CAS  PubMed  Google Scholar 

  9. Kanamori K (2016) In vivo N-15 MRS study of glutamate metabolism in the rat brain. Anal Biochem 16:30263–30269

    Google Scholar 

  10. Rothman DL, De Feyter HM, de Graaf RA et al (2011) 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed 24:943–957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Spencer AE, Uchida M, Kenworthy T et al (2014) Glutamatergic dysregulation in pediatric psychiatric disorders: a systematic review of the magnetic resonance spectroscopy literature. J Clin Psychiatry 75(11):1226–1241

    Article  PubMed  Google Scholar 

  12. Treen D, Batlle S, Mollà L et al (2016) Are there glutamate abnormalities in subjects at high risk mental state for psychosis? A review of the evidence. Schizophr Res 171(1–3):166–175

    Article  PubMed  Google Scholar 

  13. Van den Berg CJ, Krzalic L, Mela P et al (1969) Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem J 113:281–290

    Article  PubMed  Google Scholar 

  14. Berl S, Nicklas WJ, Clarke DD (1970) Compartmentation of citric acid cycle metabolism in brain: labelling of glutamate, glutamine, aspartate and GABA by several radioactive tracer metabolites. J Neurochem 17:1009–1015

    Article  CAS  PubMed  Google Scholar 

  15. Hertz L (1979) Functional interactions between neurons and astrocytes: I. Turnover and metabolism of putative amino acid transmitters. Prog Neurobiol 13:277–323

    Article  CAS  PubMed  Google Scholar 

  16. Shen J, Petersen KF, Behar KL et al (1999) Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci U S A 96:8235–8240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shen J (2006) 13C magnetic resonance spectroscopy studies of alterations in glutamate neurotransmission. Biol Psychiatry 59:883–887

    Article  CAS  PubMed  Google Scholar 

  18. Niciu MJ, Kelmendi B, Sanacora G (2012) Overview of glutamatergic neurotransmission in the nervous system. Pharmacol Biochem Behav 100(4):656–664

    Article  CAS  PubMed  Google Scholar 

  19. Danbolt NC, Storm-Mathisen J, Kanner BI (1992) An [Na+-K+]coupled l-glutamate transporter purified from rat brain is located in glial cell processes. Neuroscience 51:295–310

    Article  CAS  PubMed  Google Scholar 

  20. Rothstein JD, Dykes-Hoberg M, Pardo CA et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16(3):675–686

    Article  CAS  PubMed  Google Scholar 

  21. Ottersen OP, Zhang N, Walberg F (1992) Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum. Neuroscience 46:519–534

    Article  CAS  PubMed  Google Scholar 

  22. Sibson NR, Dhankhar A, Mason GF et al (1997) In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci U S A 94:2699–2704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shen J, Sibson NR, Cline G, Behar KL et al (1998) 15N-NMR spectroscopy studies of ammonia transport and glutamine synthesis in the hyperammonemic rat brain. Dev Neurosci 20:434–443

    Article  CAS  PubMed  Google Scholar 

  24. Patel AB, de Graaf RA, Mason GF et al (2004) Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J Cereb Blood Flow Metab 24(9):972–985

    Article  CAS  PubMed  Google Scholar 

  25. Gruetter R, Seaquist ER, Kim S et al (1998) Localized In Vivo 13C-NMR Of Glutamate Metabolism In The Human Brain: Initial Results At 4 Tesla. Dev Neurosci 20:380–388

    Article  CAS  PubMed  Google Scholar 

  26. Lebon V, Petersen KF, Cline GW et al (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

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Shen J, Rothman DL (2002) Magnetic resonance spectroscopic approaches to studying neuronal: glial interactions. Biol Psychiatry 52:694–700

    Article  CAS  PubMed  Google Scholar 

  28. Gruetter R (2002) In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism. Neurochem Int 41(2–3):143–154

    Article  CAS  PubMed  Google Scholar 

  29. Sibson NR, Dhankhar A, Mason GF et al (1998) Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 95:316–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stelmashook EV, Isaev NK, Lozier ER et al (2011) Role of glutamine in neuronal survival and death during brain ischemia and hypoglycemia. Int J Neurosci 121:415–422

    Article  CAS  PubMed  Google Scholar 

  31. de Graaf RA (1998) In vivo NMR spectroscopy. John Wiley & Sons, Chichester, UK

    Google Scholar 

  32. Choi IY, Lee SP, Merkle H et al (2004) Single-shot two-echo technique for simultaneous measurement of GABA and creatine in the human brain in vivo. Magn Reson Med 51(6):1115–1121

    Article  CAS  PubMed  Google Scholar 

  33. Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13(3):129–153

    Article  CAS  PubMed  Google Scholar 

  34. Cox IJ (1996) Development and applications of in vivo clinical magnetic resonance spectroscopy. Prog Biophys Mol Biol 65(1–2):45–81

    Article  CAS  PubMed  Google Scholar 

  35. Hurd R, Sailasuta N, Srinivasan R et al (2004) Measurement of brain glutamate using TE-averaged PRESS at 3T. Magn Reson Med 51:435–440

    Article  CAS  PubMed  Google Scholar 

  36. Ramadan S, Lin A, Stanwell P (2013) Glutamate and glutamine: a review of in vivo MRS in the human brain. NMR Biomed 26(12):1630–1646

    Article  CAS  PubMed  Google Scholar 

  37. Srinivasan R, Sailasuta N, Hurd R et al (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 128(Pt 5):1016–1025

    Article  PubMed  Google Scholar 

  38. Zhang Y, Shen J (2016) Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla. Magn Reson Med 76(3):725–732

    Article  CAS  PubMed  Google Scholar 

  39. de Graaf RA, Rothman DL, Behar KL (2011) State of the art direct 13C and indirect 1H-[13C] NMR spectroscopy in vivo. A practical guide. NMR Biomed 24:958–972

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Li S, Chen Z, Zhang Y et al (2005) In vivo single-shot, proton-localized 13C MRS of rhesus monkey brain. NMR Biomed 18:560–569

    Article  CAS  PubMed  Google Scholar 

  41. Gruetter R, Novotny EJ, Boulware SD et al (1994) Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J Neurochem 63(4):1377–1385

    Article  CAS  PubMed  Google Scholar 

  42. Li S, Yang J, Shen J (2007) Novel strategy for cerebral 13C MRS using very low RF power for proton decoupling. Magn Reson Med 57(2):265–271

    Article  CAS  PubMed  Google Scholar 

  43. Li S, Zhang Y, Ferraris Araneta M et al (2012) In vivo detection of 13C isotopomer turnover in the human brain by sequential infusion of 13C labeled substrates. J Magn Reson 218:16–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sibson NR, Mason GF, Shen J et al (2001) In vivo 13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J Neurochem 76:975–989

    Article  CAS  PubMed  Google Scholar 

  45. Deelchand DK, Nelson C, Shestov AA et al (2009) Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6-13C2]glucose and [1,2-13C2]acetate. J Magn Reson 196(2):157–163

    Article  CAS  PubMed  Google Scholar 

  46. Yang J, Shen J (2009) Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling between neurons and astroglia. J Neural Transm (Vienna) 116(3):291–300

    Article  CAS  Google Scholar 

  47. Leibfritz D, Dreher W (2001) Magnetization transfer MRS. NMR Biomed 14(2):65–76

    Article  CAS  PubMed  Google Scholar 

  48. McKenna MC, Waagepetersen HS, Schousboe A et al (2006) Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools. Biochem Pharmacol 71:399–407

    Article  CAS  PubMed  Google Scholar 

  49. Shen J (2005) In vivo carbon-13 magnetization transfer effect. Detection of aspartate aminotransferase reaction. Magn Reson Med 54:1321–1326

    Article  PubMed  Google Scholar 

  50. Xu S, Shen J (2009) Studying enzymes by in vivo C magnetic resonance spectroscopy. Prog Nucl Magn Reson Spectrosc 55(3):266–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gruetter R (1993) Automatic, localized in vivo adjustment of all first- and second-order shim coils. Magn Reson Med 29(6):804–811

    Article  CAS  PubMed  Google Scholar 

  52. Shen J, Rothman DL, Hetherington HP et al (1999) Linear projection method for automatic slice shimming. Magn Reson Med 42(6):1082–1088

    Article  CAS  PubMed  Google Scholar 

  53. Bottomley PA (1987) Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 508:333–348

    Article  CAS  PubMed  Google Scholar 

  54. Brateman L (1986) Chemical shift imaging: a review. AJR Am J Roentgenol 146(5):971–980

    Article  CAS  PubMed  Google Scholar 

  55. Juchem C, Logothetis NK, Pfeuffer J (2005) High-resolution 1H chemical shift imaging in the monkey visual cortex. Magn Reson Med 54:1541–1546

    Article  PubMed  Google Scholar 

  56. Adriany G, Gruetter R (1997) A half-volume coil for efficient proton decoupling in humans at 4 tesla. J Magn Reson 125(1):178–184

    Article  CAS  PubMed  Google Scholar 

  57. Li S, An L, Yu S et al (2016) (13)C MRS of human brain at 7 Tesla using [2-(13)C]glucose infusion and low power broadband stochastic proton decoupling. Magn Reson Med 75(3):954–961

    Article  CAS  PubMed  Google Scholar 

  58. van Eijsden P, Behar KL, Mason GF et al (2010) In vivo neurochemical profiling of rat brain by 1H-[13C] NMR spectroscopy: cerebral energetics and glutamatergic/GABAergic neurotransmission. J Neurochem 112(1):24–33

    Article  PubMed  CAS  Google Scholar 

  59. Xiang Y, Shen J (2011) Simultaneous detection of cerebral metabolism of different substrates by in vivo 13C isotopomer MRS. J Neurosci Methods 198(1):8–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hertz L, Rothman DL (2016) Glucose, lactate, β-hydroxybutyrate, acetate, GABA, and succinate as substrates for synthesis of glutamate and GABA in the glutamine-glutamate/GABA cycle. Adv Neurobiol 13:9–42

    Article  PubMed  Google Scholar 

  61. Ross BD, Lin A, Harris K et al (2003) Clinical experience with 13C MRS in vivo. NMR Biomed 16:358–369

    Article  CAS  PubMed  Google Scholar 

  62. Mason GF, Falk Petersen K, de Graaf RA et al (2003) A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose. Brain Res Brain Res Protoc 10(3):181–190

    Article  CAS  PubMed  Google Scholar 

  63. Lee D, Marcinek D (2009) Noninvasive in vivo small animal MRI and MRS: basic experimental procedures. J Vis Exp 20(32). pii: 1592. doi:10.3791/1592

  64. Li S, Shen J (2005) Integrated RF probe for in vivo multinuclear spectroscopy and functional imaging of rat brain using an 11.7 Tesla 89 mm bore vertical microimager. MAGMA 18(3):119–127

    Article  CAS  PubMed  Google Scholar 

  65. Ennis K, Deelchand DK, Tkac I et al (2011) Determination of oxidative glucose metabolism in vivo in the young rat brain using localized direct-detected 13C NMR spectroscopy. Neurochem Res 36(11):1962–1968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  67. Bluml S, Moreno-Torres A, Shic F et al (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed 15:1–5

    Article  CAS  PubMed  Google Scholar 

  68. 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

    CAS  PubMed  Google Scholar 

  69. Yang J, Li SS, Bacher J et al (2007) Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-13C]GABA derived from glia-specific substrate [2-13C]acetate. Neurochem Int 50(2):371–378

    Article  CAS  PubMed  Google Scholar 

  70. Boumezbeur F, Petersen KF, Cline GW et al (2010) The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci 30(42):13983–13991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bagga P, Behar KL, Mason GF et al (2014) Characterization of cerebral glutamine uptake from blood in the mouse brain: implications for metabolic modeling of 13C NMR data. J Cereb Blood Flow Metab 34(10):1666–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Muir D, Berl S, Clarke DD (1986) Acetate and fluoroacetate as possible markers for glial metabolism in vivo. Brain Res 380:336–340

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  74. Sonnewald U, Westergaard N, Schousboe A et al (1993) Direct demonstration by [13C]NMR spectroscopy that glutamine from glia is a precursor for GABA synthesis in neurons. Neurochem Int 22:19–29

    Article  CAS  PubMed  Google Scholar 

  75. Gulanski BI, De Feyter HM, Page KA et al (2013) Increased brain transport and metabolism of acetate in hypoglycemia unawareness. J Clin Endocrinol Metab 98(9):3811–3820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chateil J, Biran M, Thiaudiere E et al (2001) Metabolism of [1-13C]glucose and [2-13C]acetate in the hypoxic rat brain. Neurochem Int 38:399–407

    Article  CAS  PubMed  Google Scholar 

  77. 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  CAS  PubMed  Google Scholar 

  78. Garcia-Espinosa MA, Garcia-Martin ML, Cerdan S (2003) Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR. NMR Biomed 16:440–449

    Article  CAS  PubMed  Google Scholar 

  79. Sonnewald U, Kondziella D (2003) Neuronal glial interaction in different neurological diseases studied by ex vivo 13C NMR spectroscopy. NMR Biomed 16:424–429

    Article  CAS  PubMed  Google Scholar 

  80. Frahm J, Bruhn H, Gyngell ML et al (1989) Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med 9(1):79–93

    Article  CAS  PubMed  Google Scholar 

  81. Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679

    Article  CAS  PubMed  Google Scholar 

  82. Michaelis T, Merboldt KD, Bruhn H et al (1993) Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 187:219–227

    Article  CAS  PubMed  Google Scholar 

  83. de Graaf AA, Deutz NE, Bosman DK et al (1991) The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex. NMR Biomed 4:31–37

    Article  PubMed  Google Scholar 

  84. Lee HK, Yaman A, Nalcioglu O (1995) Homonuclear J-refocused spectral editing technique for quantification of glutamine and glutamate by 1H NMR spectroscopy. Magn Reson Med 34:253–259

    Article  CAS  PubMed  Google Scholar 

  85. Pan JW, Mason GF, Pohost GM et al (1996) Spectroscopic imaging of human brain glutamate by water-suppressed J-refocused coherence transfer at 4.1 T. Magn Reson Med 36:7–12

    Article  CAS  PubMed  Google Scholar 

  86. Thompson RB, Allen PS (1998) A new multiple quantum filter design procedure for use on strongly coupled spin systems found in vivo: its application to glutamate. Magn Reson Med 39:762–771

    Article  CAS  PubMed  Google Scholar 

  87. Thomas MA, Yue K, Binesh N et al (2001) Localized two-dimensional shift correlated MR spectroscopy of human brain. Magn Reson Med 46:58–67

    Article  CAS  PubMed  Google Scholar 

  88. Schulte RF, Trabesinger AH, Boesiger P (2005) Chemical-shift-selective filter for the in vivo detection of J-coupled metabolites at 3T. Magn Reson Med 53:275–281

    Article  CAS  PubMed  Google Scholar 

  89. Yahya A, Madler B, Fallone BG (2008) Exploiting the chemical shift displacement effect in the detection of glutamate and glutamine (Glx) with PRESS. J Magn Reson 191:120–127

    Article  CAS  PubMed  Google Scholar 

  90. Choi C, Coupland NJ, Bhardwaj PP et al (2006) Measurement of brain glutamate and glutamine by spectrally selective refocusing at 3 Tesla. Magn Reson Med 55:997–1005

    Article  CAS  PubMed  Google Scholar 

  91. Soher BJ, Pattany PM, Matson GB et al (2005) Observation of coupled 1H metabolite resonances at long TE. Magn Reson Med 53:1283–1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ernst T, Jiang CS, Nakama H et al (2010) Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging 32:1045–1105

    Article  PubMed  PubMed Central  Google Scholar 

  93. Prescot AP, Richards T, Dager SR et al (2012) Phase-adjusted echo time (PATE)-averaging 1H MRS: application for improved glutamine quantification at 2.89 T. NMR Biomed 25:1245–1252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Choi CH, Dimitrov IE, Douglas D et al (2010) Improvement of resolution for brain coupled metabolites by optimized H-1 MRS at 7 T. NMR Biomed 23:1044–1052

    Article  CAS  PubMed  Google Scholar 

  95. Slotboom J, Mehlkopf AF, Bovee WMMJ (1994) The effects of frequency-selective Rf pulses on J-coupled spin-1/2 systems. J Magn Reson A 108:38–50

    Article  CAS  Google Scholar 

  96. Yablonskiy DA, Neil JJ, Raichle ME et al (1998) Homonuclear J coupling effects in volume localized NMR spectroscopy: pitfalls and solutions. Magn Reson Med 39:169–178

    Article  CAS  PubMed  Google Scholar 

  97. Maudsley AA, Govindaraju V, Young K et al (2005) Numerical simulation of PRESS localized MR spectroscopy. J Magn Reson 173:54–63

    Article  CAS  PubMed  Google Scholar 

  98. An L, Li S, Murdoch JB et al (2015) Detection of glutamate, glutamine, and glutathione by radiofrequency suppression and echo time optimization at 7 tesla. Magn Reson Med 73(2):451–458

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  100. Engelsen B, Fonnum F (1983) Effects of hypoglycemia on the transmitter pool and the metabolic pool of glutamate in rat brain. Neurosci Lett 42:317–322

    Article  CAS  PubMed  Google Scholar 

  101. Wong KL, Tyce GM (1983) Glucose and amino acid metabolism in rat brain during sustained hypoglycemia. Neurochem Res 8:401–415

    Article  CAS  PubMed  Google Scholar 

  102. Lewis LD, Ljunggren B, Norberg K et al (1974) Changes in carbohydrate substrates, amino acids and ammonia in the brain during insulin-induced hypoglycemia. J Neurochem 23(4):659–671

    Article  CAS  PubMed  Google Scholar 

  103. Siesjö BK, Borgström L, Jóhannsson H et al (1976) Cerebral oxygenation in arterial hypoxia. Adv Exp Med Biol 75:335–342

    Article  PubMed  Google Scholar 

  104. Kanamatsu T, Tsukada Y (1994) Measurement of amino acid metabolism derived from [1-13C]glucose in the rat brain using 13C magnetic resonance spectroscopy. Neurochem Res 19:603–612

    Article  CAS  PubMed  Google Scholar 

  105. Lapidot A, Gopher A (1994) Cerebral metabolic compartmentation. Estimation of glucose flux via pyruvate carboxylase/pyruvate dehydrogenase by 13C NMR isotopomer analysis of d-[U-13C]glucose metabolites. J Biol Chem 269:27198–27208

    CAS  PubMed  Google Scholar 

  106. Bachelard H (1998) Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of neuronal/glial relationships. Dev Neurosci 20(4–5):277–288

    Article  CAS  PubMed  Google Scholar 

  107. Morris GA, Freeman R (1979) Enhancement of nuclear magnetic resonance signals by polarization transfer. J Am Chem Soc 101:760–762

    Article  CAS  Google Scholar 

  108. Doddrell DM, Pegg DT, Bendall MR (1982) Distortionless enhancement of NMR signals by polarization transfer. J Magn Reson 48:323–327

    CAS  Google Scholar 

  109. Baum J, Tycko R, Pines A (1985) Broadband and adiabatic inversion of a two-level system by phase-modulated pulses. Phys Rev A 32:3435–3447

    Article  CAS  Google Scholar 

  110. Silver MS, Joseph RI, Hoult DI (1984) Highly selective π/2 and π pulse generation. J Magn Reson 59:347–351

    CAS  Google Scholar 

  111. Garwood M, Ke Y (1991) Symmetric pulses to induce arbitrary flip angles with compensation for RF inhomogeneity and resonance offsets. J Magn Reson 94:511–525

    Google Scholar 

  112. Shaka AJ, Keeler J (1984) Broadband spin decoupling in isotropic liquids. Prog NMR Spectrosc 19:47–64

    Article  Google Scholar 

  113. Shaka AJ, Barker PB, Freeman R (1986) Cycling sidebands in broadband decoupling. J Magn Reson 67:396–401

    Google Scholar 

  114. de Graaf RA (2005) Theoretical and experimental evaluation of broadband decoupling techniques for in vivo nuclear magnetic resonance spectroscopy. Magn Reson Med 53(6):1297–1306

    Article  PubMed  CAS  Google Scholar 

  115. Li S, Zhang Y, Wang S et al (2010) 13C MRS of occipital and frontal lobes at 3 T using a volume coil for stochastic proton decoupling. NMR Biomed 23:977–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. An L, Warach S, Shen J (2011) Spectral localization by imaging using multielement receiver coils. Magn Reson Med 66(1):1–10

    Article  PubMed  PubMed Central  Google Scholar 

  117. An L, Shen J (2015) Image-guided spatial localization of heterogeneous compartments for magnetic resonance. Med Phys 42(9):5278–5286

    Article  PubMed  PubMed Central  Google Scholar 

  118. Rothman DL, Behar KL, Hetherington HP et al (1985) 1H-Observe/13C-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo. Proc Natl Acad Sci U S A 82:1633–1637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Pfeuffer J, Tkac I, Choi IY et al (1999) Localized in vivo 1H NMR detection of neurotransmitter labeling in rat brain during infusion of [1-13C] D-glucose. Magn Reson Med 41:1077–1083

    Article  CAS  PubMed  Google Scholar 

  120. Pan JW, Stein DT, Telang F et al (2000) Spectroscopic imaging of glutamate C4 turnover in human brain. Magn Reson Med 44(5):673–679

    Article  CAS  PubMed  Google Scholar 

  121. de Graaf RA, Brown PB, Mason GF et al (2003) Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy. Magn Reson Med 49:37–46

    Article  PubMed  CAS  Google Scholar 

  122. Yang J, Shen J (2006) Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla. Neuroimage 32(3):1317–1325

    Article  PubMed  Google Scholar 

  123. Boumezbeur F, Besret L, Valette J et al (2004) NMR measurement of brain oxidative metabolism in monkeys using 13C-labeled glucose without a 13C radiofrequency channel. Magn Reson Med 52:33–40

    Article  CAS  PubMed  Google Scholar 

  124. Schousboe A (2003) Role of astrocytes in the maintenance and modulation of glutamatergic and GABAergic neurotransmission. Neurochem Res 28:347–352

    Article  CAS  PubMed  Google Scholar 

  125. Gether U, Andersen PH, Larsson OM et al (2006) Neurotransmitter transporters: molecular function of important drug targets. Trends Pharmacol Sci 27:375–383

    Article  CAS  PubMed  Google Scholar 

  126. Duce IR, Keen P (1983) Selective uptake of [3H]glutamine and [3H]glutamate into neurons and satellite cells of dorsal root ganglia in vitro. Neuroscience 8:861–866

    Article  CAS  PubMed  Google Scholar 

  127. Rae C, Hare N, Bubb WA et al (2003) Inhibition of glutamine transport depletes glutamate and GABA neurotransmitter pools: further evidence for metabolic compartmentation. J Neurochem 85:503–514

    Article  CAS  PubMed  Google Scholar 

  128. Dzubow LM, Garfinkel D (1970) A simulation study of brain compartments. II. Atom-by-atom simulation of the metabolism of specifically labeled glucose and acetate. Brain Res 23:407–417

    Article  CAS  PubMed  Google Scholar 

  129. van den Berg CJ, Garfinkel D (1971) A simulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem J 123:211–218

    Article  PubMed  Google Scholar 

  130. Mason GF, Rothman DL, Behar KL et al (1992) NMR determination of the TCA cycle rate and alpha-ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab 12:434–447

    Article  CAS  PubMed  Google Scholar 

  131. Mason GF, Gruetter R, Rothman DL et al (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  CAS  PubMed  Google Scholar 

  132. Shen J, Rothman DL, Behar KL et al (2009) Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J Cereb Blood Flow Metab 29(1):108–118

    Article  CAS  PubMed  Google Scholar 

  133. Shen J (2013) Modeling the glutamate-glutamine neurotransmitter cycle. Front Neuroenergetics 5:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zhang Y, Shen J (2014) Smoothness of in vivo spectral baseline determined by mean-square error. Magn Reson Med 72(4):913–922

    Article  PubMed  Google Scholar 

  135. Lin AP, Shic F, Enriquez C et al (2003) Reduced glutamate neurotransmission in patients with Alzheimer’s disease – an in vivo 13C magnetic resonance spectroscopy study. MAGMA 16:29–42

    Article  CAS  PubMed  Google Scholar 

  136. Costa J, Fareleira F, Ascenção R et al (2011) Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: a systematic review and meta-analysis. Epilepsia 52:1280–1291

    Article  PubMed  Google Scholar 

  137. Petroff OA, Errante LD, Rothman DL et al (2002) Glutamate-glutamine cycling in the epileptic human hippocampus. Epilepsia 43:703–710

    Article  CAS  PubMed  Google Scholar 

  138. Sherwin AL (1999) Neuroactive amino acids in focally epileptic human brain: a review. Neurochem Res 24:1387–1395

    Article  CAS  PubMed  Google Scholar 

  139. Pan JW, Spencer DD, Kuzniecky R et al (2012) Metabolic networks in epilepsy by MR spectroscopic imaging. Acta Neurol Scand 126(6):411–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Pan JW, Duckrow RB, Gerrard J et al (2013) 7T MR spectroscopic imaging in the localization of surgical epilepsy. Epilepsia 54(9):1668–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work is supported by the intramural research program of the NIH, NIMH.

Author information

Authors and Affiliations

  1. Section on Magnetic Resonance Spectroscopy, NIMH/NIH, Bldg. 10, Rm. 2D51, 10 Center Drive, Bethesda, MD, 20892-1527, USA

    Jun Shen

Authors
  1. Jun Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Shen .

Editor information

Editors and Affiliations

  1. Lyon Neuroscience Research Center, University Lyon 1, Lyon, France

    Sandrine Parrot

  2. Lyon Neuroscience Research Center, University Lyon 1, Lyon, France

    Luc Denoroy

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Shen, J. (2018). NMR Spectroscopy of Brain Glutamate Function. In: Parrot, S., Denoroy, L. (eds) Biochemical Approaches for Glutamatergic Neurotransmission. Neuromethods, vol 130. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7228-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7228-9_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7227-2

  • Online ISBN: 978-1-4939-7228-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation