Journal of the Neurological Sciences
Volume 290, Issue 1 , Pages 41-47 , 15 March 2010

Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain glutamine and glutamate in a mouse model of ALS

  • Farhad Ghoddoussi

      Affiliations

    • Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
    • Department of Anesthesiology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
  • ,
  • Matthew P. Galloway

      Affiliations

    • Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
    • Department of Anesthesiology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
  • ,
  • Amruta Jambekar

      Affiliations

    • Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
  • ,
  • Monica Bame

      Affiliations

    • Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
  • ,
  • Richard Needleman

      Affiliations

    • Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
  • ,
  • William S.A. Brusilow

      Affiliations

    • Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 313 577 6659; fax: +1 313 577 2765.

Received 29 June 2009 ,Revised 24 November 2009 ,Accepted 24 November 2009.

References 

  1. Maragakis NJ, Rothstein JD. Glutamate transporters in neurologic disease. Arch Neurol. 2001;58(3):365–370
  2. Heath PR, Shaw PJ. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle Nerve. 2002;26(4):438–458
  3. Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci. 2004;27:723–749
  4. Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, et al. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry. 2008;30:1–11
  5. Eid T, Ghosh A, Wang Y, Beckstrom H, Zaveri HP, Lee TS, et al. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain. 2008;131(Pt 8):2061–2070
  6. Rothstein JD. Excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis. Adv Neurol. 1995;68:7–20discussion 1-7
  7. Shaw PJ, Ince PG. Glutamate, excitotoxicity and amyotrophic lateral sclerosis. J Neurol. 1997;244(Suppl 2):S3–S14
  8. Zarate CA, Manji HK. Riluzole in psychiatry: a systematic review of the literature. Expert Opin Drug Metab Toxicol. 2008;4(9):1223–1234
  9. Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL. Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem. 2007;100(1):73–86
  10. Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, et al. 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. 2002;22(5):1523–1531
  11. Benjamin AM, Quastel JH. Fate of L-glutamate in the brain. J Neurochem. 1974;23(3):457–464
  12. Hertz L, Dringen R, Schousboe A, Robinson SR. Astrocytes: glutamate producers for neurons. J Neurosci Res. 1999;57(4):417–428
  13. Broer S, Brookes N. Transfer of glutamine between astrocytes and neurons. J Neurochem. 2001;77(3):705–719
  14. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn Superoxide-Dismutase Gene Are Associated with Familial Amyotrophic-Lateral-Sclerosis. Nature. 1993;362(6415):59–62
  15. Siddique T, Deng HX, Hentati A, Tandon R, Pericakvance MA, Laing NG, et al. Mutations in the Cu-Zn Superoxide-Dismutase Gene in Familial Amyotrophic-Lateral-Sclerosis. Ann Neurol. 1993;34(2):303–304
  16. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 1994;264(5166):1772–1775
  17. Cooper AJ, Stephani RA, Meister A. Enzymatic reactions of methionine sulfoximine. Conversion to the corresponding alpha-imino and alpha-keto acids and to alpha-ketobutyrate and methane sulfinimide. J Biol Chem. 1976;251(21):6674–6682
  18. Swanson RA, Shiraishi K, Morton MT, Sharp FR. Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion. Stroke. 1990;21(2):322–327
  19. Fonnum F, Paulsen RE. Comparison of transmitter amino acid levels in rat globus pallidus and neostriatum during hypoglycemia or after treatment with methionine sulfoximine or gamma-vinyl gamma-aminobutyric acid. J Neurochem. 1990;54(4):1253–1257
  20. Somers DL, Beckstead RM. Chronic methionine sulfoximine administration reduces synaptosomal aspartate and glutamate in rat striatum. Neurosci Lett. 1990;115(2–3):335–340
  21. Pow DV, Robinson SR. Glutamate in some retinal neurons is derived solely from glia. Neuroscience. 1994;60(2):355–366
  22. Laake JH, Slyngstad TA, Haug FM, Ottersen OP. Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: immunogold evidence from hippocampal slice cultures. J Neurochem. 1995;65(2):871–881
  23. O'Leary-Moore SK, McMechan AP, Galloway MP, Hannigan JH. Neonatal alcohol-induced region-dependent changes in rat brain neurochemistry measured by high-resolution magnetic resonance spectroscopy. Alcohol Clin Exp Res. 2008;32(10):1697–1707
  24. Gaisler-Salomon I, Miller GM, Chuhma N, Lee S, Zhang H, Ghoddoussi F, et al. Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia. Neuropsychopharmacology. 2009;34(10):2305–2322
  25. Perrine SA, Michaels MS, Ghoddoussi F, Hyde EM, Tancer ME, Galloway MP. Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat. NMR Biomed. 2009;22(4):419–425
  26. Meister A. Glutamine synthetase from mammalian tissues. Methods Enzymol. 1985;113:185–199
  27. Franklin KB, Paxinos G. The mouse brain in stereotaxic coordinates. 3rd ed. N.Y., N.Y: Academic Press; 2008;
  28. Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci U S A. 1997;94(12):6408–6413
  29. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30(6):672–679
  30. Ronzio RA, Rowe WB, Meister A. Studies on the mechanism of inhibition of glutamine synthetase by methionine sulfoximine. Biochemistry. 1969;8(3):1066–1075
  31. Gershoff SN, Elvehjem CA. The relative effect of methionine sulfoximine on different animal species. J Nutr. 1951;45(3):451–458
  32. Blin M, Crusio WE, Hevor T, Cloix JF. Chronic inhibition of glutamine synthetase is not associated with impairment of learning and memory in mice. Brain Res Bull. 2002;57(1):11–15
  33. Cooper AJ, McDonald JM, Gelbard AS, Gledhill RF, Duffy TE. The metabolic fate of 13N-labeled ammonia in rat brain. J Biol Chem. 1979;254(12):4982–4992
  34. Cooper AJ, Vergara F, Duffy TE. Cerebral Glutamine Synthetase. In:  Hertz L,  Kvamme E,  Schousboe A editor. Glutamine, Glutamate, and GABA in the Central Nervous System. New York, N.Y: Alan R. Liss Inc; 1983;p. 77–93
  35. Garcia-Espinosa MA, Rodrigues TB, Sierra A, Benito M, Fonseca C, Gray HL, et al. Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy. Neurochem Int. 2004;45(2–3):297–303
  36. Kam K, Nicoll R. Excitatory synaptic transmission persists independently of the glutamate-glutamine cycle. J Neurosci. 2007;27(34):9192–9200
  37. Hasegawa J, Obara T, Tanaka K, Tachibana M. High-density presynaptic transporters are required for glutamate removal from the first visual synapse. Neuron. 2006;50(1):63–74
  38. Masson J, Darmon M, Conjard A, Chuhma N, Ropert N, Thoby-Brisson M, et al. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth. J Neurosci. 2006;26(17):4660–4671
  39. Brusilow WS. Is Huntington's a glutamine storage disease?. Neuroscientist. 2006;12(4):300–304
  40. Turner MR, Rabiner EA, Hammers A, Al-Chalabi A, Grasby PM, Shaw CE, et al. [11C]-WAY100635 PET demonstrates marked 5-HT1A receptor changes in sporadic ALS. Brain. 2005;128(Pt 4):896–905
  41. Sandyk R. Serotonergic mechanisms in amyotrophic lateral sclerosis. Int J Neurosci. 2006;116(7):775–826
  42. Schatz RA, Sellinger OZ. Effect of methionine and methionine sulphoximine on rat brain S-adenosyl methionine levels. J Neurochem. 1975;24(1):63–66
  43. 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(2):207–220
  44. Lewis DA, Moghaddam B. Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Arch Neurol. 2006;63(10):1372–1376
  45. Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, et al. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005;433(7021):73–77
  46. Ganel R, Ho T, Maragakis NJ, Jackson M, Steiner JP, Rothstein JD. Selective up-regulation of the glial Na+-dependent glutamate transporter GLT1 by a neuroimmunophilin ligand results in neuroprotection. Neurobiol Dis. 2006;21(3):556–567
  47. Wang R, Zhang D. Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model. Eur J Neurosci. 2005;22(9):2376–2380
  48. Kiaei M, Kipiani K, Petri S, Chen J, Calingasan NY, Beal MF. Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis. Neurodegener Dis. 2005;2(5):246–254
  49. Kiaei M, Kipiani K, Petri S, Choi DK, Chen J, Calingasan NY, et al. Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem. 2005;93(2):403–411
  50. Koh SH, Kim Y, Kim HY, Cho GW, Kim KS, Kim SH. Recombinant human erythropoietin suppresses symptom onset and progression of G93A-SOD1 mouse model of ALS by preventing motor neuron death and inflammation. Eur J Neurosci. 2007;25(7):1923–1930

PII: S0022-510X(09)00976-9

doi: 10.1016/j.jns.2009.11.013

Journal of the Neurological Sciences
Volume 290, Issue 1 , Pages 41-47 , 15 March 2010