Characterization of cerebral glutamine uptake from blood in the mouse brain: Implications for metabolic modeling of 13C NMR data

Journal of Cerebral Blood Flow and Metabolism

Volumn 34, Issue 10, 2014, Pages 1666-1672

  Bagga, Puneet ^a   Behar, Kevin L ^b   Mason, Graeme F ^b   De Feyter, Henk M ^b   Rothman, Douglas L ^b,c   Patel, Anant B ^a  

^a CENTRE FOR CELLULAR AND MOLECULAR BIOLOGY   (India)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c YALE UNIVERSITY   (United States)

Author keywords

glutamate; neurotransmitter; nuclear magnetic resonance spectroscopy

Indexed keywords

CARBON 13; GLUTAMINE;

AMINO ACID BLOOD LEVEL; AMINO ACID BRAIN LEVEL; AMINO ACID SYNTHESIS; AMINO ACID TRANSPORT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTE; BRAIN BLOOD FLOW; BRAIN CORTEX; BREATHING RATE; CITRIC ACID CYCLE; EX VIVO STUDY; IN VIVO STUDY; INFLUX RATE CONSTANT; MALE; MOUSE; NERVE CELL; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; STEADY STATE; ANIMAL; BIOLOGICAL MODEL; BLOOD; BLOOD BRAIN BARRIER; BRAIN; BRAIN CHEMISTRY; C57BL MOUSE; METABOLISM; PROCEDURES; TRANSPORT AT THE CELLULAR LEVEL; VASCULARIZATION;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; BRAIN CHEMISTRY; GLUTAMINE; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE; MICE, INBRED C57BL; MODELS, BIOLOGICAL;

EID: 84921709523     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2014.129     Document Type: Article

References (40)

1. de Graaf RA, Mason GF, Patel AB, Behar KL, Rothman DL. In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed 2003; 16: 339-357.
2. Lanz B, Gruetter R, Duarte JM. Metabolic flux and compartmentation analysis in the brain. Front Endocrinol (Lausanne) 2013; 4: 156.
3. de Graaf RA, Brown PB, Mason GF, Rothman DL, Behar KL. Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy. Magn Reson Med 2003; 49: 37-46.
4. Patel AB, de Graaf RA, Mason GF, Kanamatsu T, Rothman DL, Shulman RG et al. Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J Cereb Blood Flow Metab 2004; 24: 972-985.
5. Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL. The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA 2005; 102: 5588-5593.
6. Duarte JM, Lanz B, Gruetter R. Compartmentalized cerebral metabolism of [1,6-13C]glucose determined by in vivo 13C NMR spectroscopy at 14. 1 T. Front Neuroenergetics 2011; 3: 3.
7. Shen J, Petersen KF, Behar KL, Brown P, Nixon TW, Mason GF et al. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci USA 1999; 96: 8235-8240.
8. Dienel GA, Cruz NF. Exchange-mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways. J Neurochem 2009; 109(Suppl 1): 30-37.
9. Gruetter R, Novotny EJ, Boulware SD, Mason GF, Rothman DL, Shulman GI et al. Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J Neurochem 1994; 63: 1377-1385.
10. Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ. Simultaneous determination of the rates of the TCA cycle, glucose utilization, alphaketoglutarate/ glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab 1995; 15: 12-25.
11. Choi IY, Lei H, Gruetter R. Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo: on the correlation of total glucose consumption with glutamatergic action. J Cereb Blood Flow Metab 2002; 22: 1343-1351.
12. Oz G, Berkich DA, Henry PG, Xu Y, LaNoue K, Hutson SM et al. Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci 2004; 24: 11273-11279.
13. Serres S, Raffard G, Franconi JM, Merle M. Close coupling between astrocytic and neuronal metabolisms to fulfill anaplerotic and energy needs in the rat brain. J Cereb Blood Flow Metab 2008; 28: 712-724.
14. Ebert D, Haller RG, Walton ME. Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J Neurosci 2003; 23: 5928-5935.
15. Shen J, Rothman DL, Behar KL, Xu S. Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J Cereb Blood Flow Metab 2009; 29: 108-118.
16. Mason GF, Falk Petersen K, de Graaf RA, Kanamatsu T, Otsuki T, Shulman GI et al. A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose. Brain Res Brain Res Protoc 2003; 10: 181-190.
17. Sibson NR, Mason GF, Shen J, Cline GW, Herskovits AZ, Wall JE et al. In vivo 13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2-13C]glucose infusion. J Neurochem 2001; 76: 975-989.
18. Wang J, Jiang L, Jiang Y, Ma X, Chowdhury GM, Mason GF. Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine. J. Neurochem. 2010; 113: 1447-1458.
19. Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF. Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR. J Cereb Blood Flow Metab 2010; 30: 1200-1213.
20. Patel AB, Rothman DL, Cline GW, Behar KL. Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition. Brain Res 2001; 919: 207-220.
21. Bagga P, Chugani AN, Varadarajan KS, Patel AB. In vivo NMR studies of regional cerebral energetics in MPTP model of Parkinson's disease: recovery of cerebral metabolism with acute levodopa treatment. J Neurochem 2013; 127: 365-377.
22. Tiwari V, Ambadipudi S, Patel AB. Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain. J Cereb Blood Flow Metab 2013; 33: 1523-1531.
23. Smith QR, Momma S, Aoyagi M, Rapoport SI. Kinetics of neutral amino acid transport across the blood-brain barrier. J Neurochem 1987; 49: 1651-1658.
24. Benjamin AM, Verjee ZH, Quastel JH. Kinetics of cerebral uptake processes in vitro of L-glutamine, branched-chain L-amino acids, and L-phenylalanine: effects of ouabain. J Neurochem 1980; 35: 67-77.
25. Balcar VJ, Johnston GA. High affinity uptake of L-glutamine in rat brain slices. J Neurochem 1975; 24: 875-879.
26. Ennis SR, Kawai N, Ren XD, Abdelkarim GE, Keep RF. Glutamine uptake at the blood-brain barrier is mediated by N-system transport. J Neurochem 1998; 71: 2565-2573.
27. Nagaraja TN, Brookes N. Glutamine transport in mouse cerebral astrocytes. J Neurochem 1996; 66: 1665-1674.
28. Schousboe A, Hertz L, Svenneby G, Kvamme E. Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J Neurochem 1979; 32: 943-950.
29. Su TZ, Campbell GW, Oxender DL. Glutamine transport in cerebellar granule cells in culture. Brain Res 1997; 757: 69-78.
30. Cole JT, Sweatt AJ, Hutson SM. Expression of mitochondrial branched-chain aminotransferase and alpha-keto-acid dehydrogenase in rat brain: implications for neurotransmitter metabolism. Front Neuroanat 2012; 6: 18.
31. Choi IY, Gruetter R. In vivo 13C NMR assessment of brain glycogen concentration and turnover in the awake rat. Neurochem Int 2003; 43: 317-322.
32. Tiwari V, Veeraiah P, Subramaniam V, Patel AB. Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain. J Neurochem 2013; 128: 628-640.
33. Waniewski RA, Martin DL. Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 1998; 18: 5225-5233.
34. Lanz B, Xin L, Millet P, Gruetter R. In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1H-[13C] MRS at 14. 1T. J Neurochem 2014; 128: 125-139.
35. Rothman DL, De Feyter HM, Maciejewski PK, Behar KL. Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes? Neurochem Res 2012; 37: 2597-2612.
36. Hertz L, Hertz E. Cataplerotic TCA cycle flux determined as glutamate-sustained oxygen consumption in primary cultures of astrocytes. Neurochem Int 2003; 43: 355-361.
37. Kanamori K, Ross BD. Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, alpha-(methylamino)isobutyrate. J Neurochem 2004; 90: 203-210.
38. Broer S, Brookes N. Transfer of glutamine between astrocytes and neurons. J Neurochem 2001; 77: 705-719.
39. Cangiano C, Cardelli-Cangiano P, James JH, Rossi-Fanelli F, Patrizi MA, Brackett KA et al. Brain microvessels take up large neutral amino acids in exchange for glutamine. Cooperative role of Na-dependent and Na-independent systems. J Biol Chem 1983; 258: 8949-8954.
40. Matsuo H, Tsukada S, Nakata T, Chairoungdua A, Kim DK, Cha SH et al. Expression of a system L neutral amino acid transporter at the blood-brain barrier. Neuroreport 2000; 11: 3507-3511.