Amyotrophic Lateral Sclerosis, Glutamate, and Oxidative Stress

Andreas Plaitakis and P. Shashidharan
Mount Sinai School of Medicine
One Gustave L. Levy Place
New York, NY 10029
phone:  212-241-7310



REFERENCES

1. Allaoua H, Chaudieu I, Krieger C, et al. Alterations in spinal cord excitatory amino acid receptors in amyotrophic lateral sclerosis. Brain Res 1992;579:169172.

2. Aoki, M., Lin, C. L., Rothstein, J. D., Geller, B. A., Hosler, B. A., Munsat, T. L., Horvitz, H. R. and Brown, R., Jr. Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis. Ann Neurol.1998;43: 645-653

3. Arriza, J. L., Fairman, W. A., Wadiche, J. I., Murdoch, G. H., Kavanaugh, M. P. and Amara, S. G. (1994). Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci. 1994; 14:5559-5569.

4. Arriza, J. L., Eliasof, S., Kavanaugh, M. P. and Amara, S. G. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A.1997; 94: 4155-4160

5. Babu GN, Bawari M, Mathur VN, Kalita J, Mistra UK. Blood glutamate levels in patients with motor neuron disease. Clin Chim Acta 1998; 273:195-200

6. Battaglioli G, Martin DL, Plummer J, Messer A. Synaptosomal glutamate uptake declines progressively in the spinal cord of a mutant mouse with motor neuron disease. J Neurochem 1993;60: 15671569.

7. Blin O, Desnuelle C, Guelton C, et al. Clinique des maladies du systeme nerveux et de l'appareil locomoteur. Rev Neurol 1991;147:292294.

8. Block, W., Karitzky, J., Traber, F., Pohl, C., Keller, E., Mundegar, R. R., Lamerichs, R., Rink, H., Ries, F., Schild, H. H. and Jerusalem, F. Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements. Arch Neurol. 1998; 55: 931-936.

9. Bristol, L. A. and Rothstein, J. D. Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann Neurol.1996; 39: 676-679.

10. Browne, S. E., Bowling, A. C., Baik, M. J., Gurney, M., Brown, R., Jr. and Beal, M. F. (1998). Metabolic dysfunction in familial, but not sporadic, amyotrophic lateral sclerosis. J Neurochem.71, 281-287

11. Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S. D., Ohama, E., Reaume, A. G., Scott, R. W. and Cleveland, D. W. (1998). Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science.281, 1851-1854

12. Budai D, Wilcox GL, Larsen AA. Enhancement of NMDA-evoked neuronal activity by glycine in the rat spinal cord in vivo. Neurosci Lett 1992;135:265268.

13. Canton T, Pratt J, Stutzmann JM, Imperato A, Boireau A. Glutamate uptake is decreased tardively in the spinal cord of FALS mice. Neuroreport 1998;3:775-8).

14. Clements JD., Lester RAJ, Tong CE and Jahr CE. The time course of glutamate in the synaptic cleft. Science 1992;258:1498-1501

15. Crow, J. P., Sampson, J. B., Zhuang, Y., Thompson, J. A. and Beckman, J. S. (1997). Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J Neurochem.69, 1936-1944

16.Constantakakis E, Plaitakis A. N-acetyl-aspartate and N-acetyl-aspartyl-glutamate are altered in amyotrophic lateral sclerosis. Ann Neurol 1988;24:478.

17. Curtis DR, Watkins JC. The excitation and depression of spinal neurons by structurally related amino acids. J Neurochem 1960; 6:117141.

18. Dalakas MC, Harazawa J, Brooks RA, et al. Lowered cerebral glucose utilization in amyotrophic lateral sclerosis. Ann Neurol 1987;22:580586.

19. Durham, H. D., Roy, J., Dong, L. and Figlewicz, D. A. (1997). Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS. J Neuropathol Exp Neurol.56, 523-530

20. Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P. and Amara, S. G. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature. 1995; 375; 599-603.

21. Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochemistry, 1984;42:111.

22. Fray, A. E., Ince, P. G., Banner, S. J., Milton, I. D., Usher, P. A., Cookson, M. R. and Shaw, P. J. (1998). The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study. Suppl Eur J Neurosci. 1998; 10: 2481-2489.

23. Futura A, Martin LI, Lin CL, Dykes-Hoberg M, Rothstein JD. Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience 1997;81:1031-1042.

24. Gegelashvili, G., Danbolt, N. C. and Schousboe, A. Neuronal soluble factors differentially regulate the expression of the GLT1 and GLAST glutamate transporters in cultured astroglia. J Neurochem. 1997; 69: 2612-2615

25. Gredal O, Pakkenberg B, Nielsen M. Muscarinic, N-methyl-D-aspartate (NMDA) and benzodiazepine receptor binding sites in cortical membranes from amyotrophic lateral sclerosis. J Neurol Sci. 1996; 143:121-125.

26. Ghadge, G. D., Lee, J. P., Bindokas, V. P., Jordan, J., Ma, L., Miller, R. J. Roos, R. P. (1997). Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: molecular mechanisms of neuronal death and protection. J Neurosci.1997; 17: 8756-8766.

27. Hall, E. D., Andrus, P. K., Oostveen, J. A., Fleck, T. J. and Gurney, M. E. (1998). Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J Neurosci Res.1998; 53: 66-77.

28. Ikonomidou C, Qin Qin Y, Labruyere J, Olney JW. Motor neuron degeneration induced by excitotoxin agonists has features in common with those seen in SOD-1 transgenic mouse model of amyotrophic lateral sclerosis. J. Neuropathol Exp Neurol 1996;55:211-24.

29. Iwasaki Y, Ikeda K, Kinoshita M. Plasma amino acid levels in patients with amyotrophic lateral sclerosis. J Neurol Sci 1992; 107:219222

30. Kanai Y, Hediger MA. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 1992; 360:467471.

31. Langlais PJ, Mair RG. Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in brain. J Neurosci 1990;10:16641667.

32. Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J and Danbolt NC. Differential expression of two glial glutamate transporters in rat brain: quantitative and immunocytochemical observations. J Neurosci 1995; 15:1835-53

33. Levy LM, Lehre KP, Walaas I, Storm-Mathisen J, Danbolt NC. Downregulation of glial glutamate transporters after glutamatergic denervation in the rat brain. Eur J Neurosci 1995; 7:2036-41

34. Lin, C. L., Bristol, L. A., Jin, L., Dykes-Hoberg, M., Crawford, T., Clawson, L. and Rothstein, J. D. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 1998; 20: 589-602.

35. Lucas DR, Newhouse JP. The toxic effect of sodium L-glutamate on the inner layer of the retina. AMA Arch Ophthalmol 1957;58:193204.

36. Malessa S, Leigh PN, Bertel O, Sluga E, Hornykiewicz O. Amyotrophic lateral sclerosis, glutamate dehydrogenase and transmitter amino acids in the spinal cord. J Neurol Neurosurg Psychiatry 1991;54:984988.

37. Mayer ML, Ladislav V Jr, Clements J. Regulation of NMDA receptor desensitization in mouse hippocampal neurons by glycine. Nature 1989;338:425427.

38. McNamara J, Fridovich I. Did radicals strike Lou Gehrig? Nature 1993;362:2021.

39. Medina L, Figueredo-Cardenas G, Rothstein JD, Reiner A. Differential abundance of glutamate transporter subtypes in amyotrophic lateral sclerosis (ALS)-vulnerable versus ALS-resistant brain stem motor cell groups. Exp Neurol 1996; 14:287-95

40. Milton ID, Banner SJ, Ince PG, Piggott NH, Fray AE, Thatcher N, Horne CH, Shaw PJ. Expression of the glial glutamate transporter EAAT2 in human CNS: an immunocytochemical study. Brain Res Mol Brain Res. 1977; 52:17-31

41. Mitchell JJ, Anderson KJ. Quantative autoradiographic analysis of excitatory amino acid receptors receptors in the cat spinal cord. Neurosci Lett 1991; 124:269-272

42. Morrison BM, Janssen WG, Gordon WJ, Morrison JH. Light and electron microscopic distribution of the AMPA receptor subunit, GluR2, in the spinal cord of control and G86R mutant superoxide dismut ase transgenic mice . J Comp Neurol 1998; 395:523-34.

43. Mourelatos Z, Yachnis A, Rorke L, et al. The Golgi apparatus of motor neurons in amyotrophic lateral sclerosis. Ann Neurol 1993;33:608615.

44. Murphy TH, Miyamoto M, Sastre A, et al. Glutamate toxicity in neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron 1989;2:15471558.

45. Nag S, Riopelle RJ. Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat. Acta Neuropathol 1990;81:713.

46. Nagai, M., Abe, K., Okamoto, K. and Itoyama, Y. Identification of alternative splicing forms of GLT-1 mRNA in the spinal cord of amyotrophic lateral sclerosis patients. Neurosci Lett.1008; 244:165-168.

47. Nakanishi S. Molecular diversity of glutamate receptors and implications for brain function. Science 1992;258:597603.

48. Nicklas WJ, Krespan B, Berl S. Effect of kainate on ATP levels and glutamate metabolism in cerebellar slices. Eur J Pharmacol 62:209215.

49. O'Brien RJ, Fischbach GD. Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists. J Neurosci 1986;6:32903296.

50. Olney JW, Ho OL, Rhee V. Cytotoxic effects of acidic and sulfur containing amino acids on the infant mouse central nervous system. Exp Brain Res 1971;14:6176.

51.Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in mammalian central nervous system. Prog Neurobiol 1998; 54:581-618.

52. Perl TM, Bedard L, Kosatsky T, et al. An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 1990;322:177517780.

53. Perry TL, Hansen S, Jones K. Brain glutamate deficiency in amyotrophic lateral sclerosis. Neurology 1987;37:18451848.

54. Perry TL, Krieger C, Hansen S, Eisen A. Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid. Ann Neurol 1990;28:1217.

55. Perry TL, Hansen S. What excitotoxin kills striatal neurons in Huntington's disease? Clues from biochemical studies. Neurology 1990;40:2024.

56. Pioro EP, Preul MC, Antel JP, Arnold DL. 1M-magnetic resonance spectroscopy demonstrates decreased N-acetyl-aspartate in the cerebrum of patients with amyotrophic lateral sclerosis. Neurology 1993;44(Suppl 2):405P.

57. Pioro, E. P. MR spectroscopy in amyotrophic lateral sclerosis/motor neuron disease. J Neurol Sci.1997; 152: S49-53.

58. Pines G, Danbolt NC, Bjoras M, et al. Cloning and expression of a rat brain L-glutamate transporter. Nature 1992;360:464467.

59. Plaitakis A, Nicklas WJ, Berl S. Alterations in uptake and metabolism of aspartate and glutamate in brain of thiamine deficient animals. Brain Res 1979;171:489502.

60. Plaitakis A, Berl S, Yahr MD. Abnormal glutamate metabolism in an adult-onset degenerative neurological disorder. Science 1982; 216:193196.

61. Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol 1987;22:5755759.

62. Plaitakis A, Constantakakis E, Smith J. The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann Neurol 1988;24:446449.

63. Plaitakis A. Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis. A hypothesis. Ann Neurol 1990;28:38.

64. Plaitakis A, Mandeli J, Fesdjian CO, Smith J, Sivak M. Dysregulation of glutamate metabolism in ALS: correlation with gender and disease type. Neurology 1990;41(Suppl 1):392393.

65. Plaitakis A, Constantakakis E. Altered metabolism of excitatory amino acids, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate in amyotrophic lateral sclerosis. Brain Res Bull 1993;30:381386.

66. Plaitakis A, Shashidharan P. Amyotrophic lateral sclerosis, glutamate and oxidative stress. Psychopharmacology. In Bloom FE, Kupfer DJ, edts. The Fourth Generation of Progress 1995 pp 1531-43.

67. Regan RF, Choi DW. Glutamate neurotoxicity in spinal cord cell culture. Neuroscience 1991;43:585591.

68. Rosen DR, Siddique T, Patterson D, et al. Mutations in CU/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993;362:5962.

69. Rothstein JD, Tsai G, Kuncl RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol 1990;28:1825.

70. Rothstein JD, Kuncl R, Chaudhry V, et al. Excitatory amino acids in amyotrophic lateral sclerosis: an update. Ann Neurol 1991;30:224225.

71. Rothstein JD, Martin LJ, Kuncl RW. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 1992;326:14641468.

72. Rothstein JD, Jin L, Dykes-Hoberg M, Kuncl RW. Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc Natl Acad Sci USA 1993;90:65916595.

73. Rothstein, J. D., Van Kammen, M., Levey, A. I., Martin, L. J. and Kuncl, R. W. (1995). Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol.1995; 38: 73-84.

74. Samarasinghe S, Virgo L, de Belleroche J. Distribution of N-methyl-D-aspartate glutamate receptor subunit NR2 in control and amyotrophic lateral sclerosis spinal cord. Brain Res 1996; 727:233-237.

75. Shashidharan P, Plaitakis A. Cloning and characterization of a glutamate transporter cDNA from human cerebellum. Biochim Biophys Acta 1993;1216:161164.

76. Shashidharan, P., Huntley, G. W., Meyer, T., Morrison, J. H. and Plaitakis, A. Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain. Brain Res.1994; 662: 245-250.

77. Shashidharan, P., Wittenberg, I. and Plaitakis, A. Molecular cloning of human brain glutamate/aspartate transporter II. Biochim Biophys Acta 1994.1191: 393-396.

78. Shashidharan P, Huntley GW, Murray J, Walsh MJ, Buku A, Moran T, Morrison JH and Plaitakis A. Immunohistochemical Localization of Neuron-specific Glutamate Transporter (EAAC1) in rat brain and spinal cord revealed by a novel Monoclonal Antibody Brain Res. 1997; 773:139-148.

79. Shaw PJ, Chinnery RM, Ince PG. [3H]D-aspartate binding sites in the normal spinal cord and changes in motor neuron disease: a quantitative autoradiographic study. Brain Res 1994; 665:195-201

80. Shaw PJ, Ince PG, Mathews JN, Johnson M and Candy JM. N-methyl-D-aspartate (NMDA) receptors in the spinal cord and motor cortex in motor neuron disease: a quantitative autoradiographic study using [3H]MK-801. Brain Res 1994:637:297-302.

81. Shaw PJ, Forrset V, Ince PG, Richardson JP and Wastell HJ. CSF and plasma amino acid levels in motor neuror disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 1995; 4:209-216.

82. Shaw, P. J., Ince, P. G., Falkous, G. and Mantle, D. Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol.1995; 38: 691-695

83. Sies H, ed. Oxidative stress London: Academic Press, 1985;273303.

84. Storck T, Shulte S, Hofmann K, Stoffel W. Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci USA 1992;89:1095510959.

85. Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahashi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., Okuyama, S., Kawashima, N., Hori, S., Takimoto, M. and Wada, K.. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science.1997; 276: 1699-1702

86. Thomson AM, Walker VE, Flynn DM. Glycine enhances NMDA-receptor mediated synaptic potentials in neocortical slices. Nature 1989;338:422424.

87. Tsai GC, Stauch-Sluser B, Sim L, et al. Reductions in acidic amino acids and N-acetylaspartylglutamate in amyotrophic lateral sclerosis. Brain Res 1991;556:151156.

88. Virgo L, de Belleroche J. Induction of the immediate early gene c-jun in human spinal cord in amyotrophic lateral sclerosis with concomitant loss of NMDA receptor NR-1 and glycine transporter mRNA. Brain Res 1995; 676:196-204

89. Waelsch H, Berl S, Rossi CA, Clarke DD, Purpura DP. Quantitative aspects of CO2 fixation in mammalian brain in vivo. J Neurochem, 1964;11:717728.

90. Wiedemann, F. R., Winkler, K., Kuznetsov, A. V., Bartels, C., Vielhaber, S., Feistner, H. and Kunz, W. S. Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci.1998; 156: 65-72.

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published 2000