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Journal of Neurocytology

, Volume 30, Issue 12, pp 945–955 | Cite as

Chronological changes of N-methyl-D-aspartate receptors and excitatory amino acid carrier 1 immunoreactivities in CA1 area and subiculum after transient forebrain ischemia

  • Tae-Cheon Kang
  • In Koo Hwang
  • Seung-Kook Park
  • Sung-Jin An
  • Dae-Kun Yoon
  • Seung Myung Moon
  • Yoon-Bok Lee
  • Heon-Soo Sohn
  • Sa Sun Cho
  • Moo Ho Won
Article

Abstract

We investigated changes of immunoreactivities of N-methyl-D-aspartate receptor (NR) and of excitatory amino acid carrier 1 (EAAC-1), the neuronal glutamate transporter, in the vulnerable CA1 area and the less vulnerable subiculum of the gerbil hippocampus at various times following transient forebrain ischemia. At 30 min after ischemia-reperfusion, the intensity of NR immunoreactivity increased markedly in neurons of CA1 and subiculum, particularly NR2A/B, while EAAC-1 immunoreactivity was reduced in CA1. At 3 hr after reperfusion, the density of NR1 immunoreactivity markedly decreased in CA1. In contrast EAAC-1 immunoreactivity increased in CA1 and in the subiculum. At 12 hr after reperfusion, the decrease of NR1 immunoreactivity was not detected whereas EAAC-1 immunoreactivities in the CA1 area were intensified. In the subiculum, both NR subunits immunoreactivities decreased significantly, in contrast to the maintenance of EAAC-1 immunoreactivity. At 24 hr after reperfusion, both NR2A/B and EAAC-1 immunoreactivities decreased markedly in CA1 and subiculum. We tentatively suggest that the increase of NR immunoreactivity in CA1 at early times after ischemia-reperfusion may increase the delayed neuronal death, and that the increase or maintenance of EAAC-1 immunoreactivity at early times after ischemia-reperfusion may be an important factor in survival of neurons.

Keywords

Ischemia Glutamate Early Time Neuronal Death Glutamate Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Attwell, D., Barbour, B. & Szatkowski, M. (1993) Nonvesicular release of neurotransmitter. Neuron 11, 401–407.Google Scholar
  2. Auer, R. N. & Coulter, K. C. (1994) The nature and time course of neuronal vacuolation induced by the N-methyl-D-aspartate antagonist MK-801. Acta Neuropathologica 87, 1–7.Google Scholar
  3. Balcar, V. J. & Johnston, G. A. The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices. Journal of Neurochemistry 19, 2657–2666.Google Scholar
  4. Benveniste, H., Jorgensen, M. B., Diemer, N. H. & Hansen, A. J. (1988) Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. Acta Neurologica Scandinavica 78, 529–536.Google Scholar
  5. Buchs, P. A., Stoppini, L. & Muller, D. (1993) Structural modifications associated with synaptic development in area CA1 of rat hippocampal organotypic cultures. Developmental Brain Research 71, 81–91.Google Scholar
  6. Choi, D. W. (1992) Excitotoxic cell death. Journal of Neurobiology 23, 1261–1276.Google Scholar
  7. Choi, D. W. (1995) Calcium: Still center-stage in hypoxicischemic neuronal death. Trends in Neurosciences 18, 58–60.Google Scholar
  8. Deshpande, J. K., Siesjo, B. K. & Wieloch, T. (1987) Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism 7, 89–95.Google Scholar
  9. Dienel, G. A. (1984) Regional accumulation of calcium in postischemic rat brain. Journal of Neurochemistry 43, 913–925.Google Scholar
  10. Fujita, H., Sato, K., Wen, T. C., Peng, Y. & Sakanaka, M. (1999) Differential expressions of glycine transporter 1 and three glutamate transporter mRNAin the hippocampus of gerbils with transient forebrain ischemia. Journal of Cerebral Blood Flow & Metabolism 19, 604–615.Google Scholar
  11. Furuta, S., Ohta, S., Hatakeyama, T., Nakamura, K. & Sakaki, S. (1993) Recovery of protein synthesis in tolerance-induced hippocampal CA1 neurons after transient forebrain ischemia. Acta Neuropathologica 86, 329–336.Google Scholar
  12. Gass, P., Muelhardt, C., Sommer, C., Becker, C. M. & Kiessling, M. (1993) NMDA and glycine receptor mRNA expression following transient global ischemia in the gerbil brain. Journal of Cerebral Blood Flow & Metabolism 13, 337–341.Google Scholar
  13. Gottlieb, M., Domercq, M. & Matute, C. (2000) Altered expression of the glutamate transporter EAAC1 in neurons and immature oligodendrocytes after transient forebrain ischemia. Journal of Cerebral Blood Flow & Metabolism 20, 678–687.Google Scholar
  14. Hediger, M. A., Kanai, Y., You, G. & Nussberger, S. (1995) Mammalian ion-coupled solute transporters. Journal of Physiology 482, 7S–17S.Google Scholar
  15. Hollmann, M. & Heinemann, S. (1994) Cloned glutamate receptors. Annual Review of Neuroscience 17, 31–108.Google Scholar
  16. Hollmann, M., Boulter, J., Maron, C. & Heinemann, S. (1994) Molecular biology of glutamate receptors. Potentiation of N-methyl-D-aspartate receptor splice variants by zinc. Renal Physiology and Biochemistry 17, 182–183.Google Scholar
  17. Hsu, J. C., Zhang, Y., Takagi, N., Gurd, J. W., Wallace, M. C., Zhang, L. & Eubanks, J. H. (1998) Decreased expression and functionality ofNMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism 18, 768–775.Google Scholar
  18. Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., Masu, M. & Nakanishi, S. (1993) Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. Journal of Biological Chemistry 268, 2836–2843.Google Scholar
  19. Jabaudon, D., Scanziani, M., Gahwiler, B. H. & Gerber, U. (2000) Acute decrease in net glutamate uptake during energy deprivation. Proceedings of the National Academy of Sciences of the USA 97, 5610–5615.Google Scholar
  20. Kanai, Y. & Hediger, M. A. (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467–471.Google Scholar
  21. Kirino, T. (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Research 239, 57–69.Google Scholar
  22. Krupp, J. J. Vissel, B. Heinemann, S. F. & Westbrook, G. L. (1996) Calcium-dependent inactivation of recombinant N-methyl-D-aspartate receptors is NR2 subunit specific. Molecular Pharmacology 50, 1680–1688.Google Scholar
  23. Legendre, P., Rosenmund, C. & Westbrook, G. L. (1993) Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium. Journal of Neuroscience 13, 674–684.Google Scholar
  24. Lehre, K. P., Levy, L. M., Ottersen, O. P., Stormmathisen, J. & Danbolt, N. C. (1995) Differential expression of two glial glutamate transporters in the rat brain: Quantitative and immunocytochemical observations. Journal of Neuroscience 15, 1835–1853.Google Scholar
  25. Lesiuk, H., Sutherland, G., Peeling, J., Butler, K. & Saunders, J. (1991) Effect of U74006F on forebrain ischemia in rats. Stroke 22, 896–901.Google Scholar
  26. Mcilhinney, R. A., Molnar, E., Atack, J. R. & Whiting, P. J. (1996) Cell surface expression of the human N-methyl-D-aspartate receptor subunit 1a requires the co-expression of the NR2A subunit in transfected cells. Neuroscience 70, 989–997.Google Scholar
  27. Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540.Google Scholar
  28. Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B. & Seeburg, P. H. (1992) Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science 256, 1217–1221.Google Scholar
  29. Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N. & Nakanishi, S. (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 31–37.Google Scholar
  30. Nakanishi, S. (1992) Molecular diversity of glutamate receptors and implications for brain function. Science 258, 597–603.Google Scholar
  31. Nellgard, B. & Wieloch, T. (1992) Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following transient severe cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism 12, 2–11.Google Scholar
  32. Okabe, S., Miwa, A. & Okado, H. (1999) Alternative splicing of the C-terminal domain regulates cell surface expression of the NMDA receptor NR1 subunit. Journal of Neuroscience 19, 7781–7792.Google Scholar
  33. Paschen, W. (1996) Glutamate excitotoxicity in transient global cerebral ischemia. Acta Neurobiologiae Experimentalis 56, 313–322.Google Scholar
  34. Petito, C. K., Feldmann, E., Pulsinelli, W. A. & Plum, F. (1987) Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 37, 1281–1286.Google Scholar
  35. Pines, G., Danbolt, N. C., Bjoras, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Stormmathisen, J., Seeberg, E. & Kanner, B. I. (1992) Cloning and expression of a rat brain L-glutamate transporter. Nature 360, 464–467.Google Scholar
  36. Pulsinelli, W., Sarokin, A. & Buchan, A. (1993) Antagonism of the NMDA and non-NMDA receptors in global versus focal brain ischemia. Progress in Brain Research 96, 125–135.Google Scholar
  37. Pulsinelli, W. A., Brierley, J. B. & Plum, F. (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Annals of Neurology 11, 491–498.Google Scholar
  38. Rauen, T., Jeserich, G., Danbolt, N. C. & Kanner, B. I. (1992) Comparative analysis of sodiumdependent L-glutamate transport of synaptosomal and astroglial membrane vesicles from mouse cortex. FEBS Letters 312, 15–20.Google Scholar
  39. Robinson, M. B., Hunter-Ensor, M. & Sinor, J. (1991) Pharmacologically distinct sodium-dependent L-[3H]glutamate transport processes in rat brain. Brain Research 544, 196–202.Google Scholar
  40. Robinson, M. B., Sinor, J. D., Dowd, L. A. & Kerwin, JR. J. F. (1993) Subtypes of sodiumdependent high-affinity L-[3H]glutamate transport activity: Pharmacologic specificity and regulation by sodium and potassium. Journal of Neurochemistry 60, 167–179.Google Scholar
  41. Rothman, S. M. & Olney, J. W. (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Annals of Neurology 19, 105–111.Google Scholar
  42. Rothman, S. M. & Olney, J. W. (1995) Excitotoxicity and the NMDA receptor-still lethal after eight years. Trends in Neurosciences 18, 57–58.Google Scholar
  43. Scharfman, H. E. & Schwartzkroin, H. E. (1989) Protection of dentate hilar cells from prolonged stimulation by intracellular calcium chelation. Science 246, 257–260.Google Scholar
  44. Storck, T., Schulte, S., Hofmann, K. & Stoffel, W. (1992) Structure, expression and functional analysis of the Na+-dependent glutamate/aspartate transporter from rat brain. Proceedings of the National Academy of Sciences of the USA 89, 10955–10959.Google Scholar
  45. Szatkowski, M. & Attwell, D. (1994) Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends in Neurosciences 17, 359–365.Google Scholar
  46. Takahashi, M., Billups, B., Rossi, D., Sarantis, M., Hamann, M. & Attwell, D. (1997) The role of glutamate transporters in glutamate homeostasis in the brain. Journal of Experimental Biology 200, 401–409.Google Scholar
  47. Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahasi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., Okuyama, S., Kawashima, N., Hori, S., Takimoto, M. & Wada, K. (1997) Epilepsy and exacerabation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276, 1699–1702.Google Scholar
  48. Thilmann, R., Xie, Y., Kleihues, P. & Kiessling, M. (1986) Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus. Acta Neuropathologica 71, 88–93.Google Scholar
  49. Wang, B., Gonzalo-Ruiz, A., Sanz, J. M., Campbell, G. & Lieberman, A. R. (2001) Glutamatergic components of the retrosplenial granular cortex in the rat. Journal of Neurocytology 30, 427–441.Google Scholar
  50. Wang, X. S., Ong, W. Y., Lee, H. K. & Huganir, R. L. (2000) A light and electron microscopic study of glutamate receptors in the monkey subthalamic nucleus. Journal of Neurocytology 29, 743–754.Google Scholar
  51. Westbrook, G. L. (1994) Glutamate receptor update. Current Opinion in Neurobiology 4, 337–346.Google Scholar
  52. Widmann, R., Weber, C., Bonnekoh, P., Schlenker, M. & Hossmann, K. A. (1992) Neuronal damage after repeated 5 minutes of ischemia in the gerbil is preceded by prolonged impairment of protein metabolism. Journal of Cerebral Blood Flow & Metabolism 12, 425–433.Google Scholar
  53. Won, M. H., Kang, T.-C., Jeon, G. S., Lee, J. C., Kim, D. Y., Choi, E. M., Lee, K. H., Choi, C. D., Chung, M. H. & Cho, S. S. (1999) Immunohistochemical detection of oxidative DNA damage induced by ischemia-reperfusion insults in gerbil hippocampus in vivo. Brain Research 836, 70–78.Google Scholar
  54. Won, M. H., Kang, T.-C., Park, S. K., Jeon, G. S., Kim, Y. W., Seo, J. H., Choi, E. M., Chung, M. H. & Cho, S. S. (2001) The alterations of N-methyl-Daspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemiareperfusion insult. Neuroscience Letters 301, 139–142.Google Scholar
  55. Xie, Y. X., Herget, T., Hallmayer, J., Starzinskipowitz, A. & Hossmann, K. A. (1989) Determination of RNA content in postischemic gerbil brain by in situ hybridization. Metabolic Brain Disease 4, 239–251.Google Scholar
  56. Ying, Z., Babb, T. L., Comair, Y. G., Bingaman, W., Bushey, M. & Touhalisky, K. (1988) Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex. Journal of Neuropathology & Experimental Neurology 57, 47–62.Google Scholar
  57. Zhang, C. & Wong-Riley, M. (1999) Expression and regulation of NMDA receptor subunit R1 and neuronal nitric oxide synthase in cortical neuronal cultures: Correlation with cytochrome oxidase. Journal of Neurocytology 28, 525–539.Google Scholar
  58. Zhang, L., Hsu, J. C., Takagi, N., Gurd, J. W., Wallace, M. C. & Eubanks, J. H. (1997) Transient global ischemia alters NMDA receptor expression in rat hippocampus: Correlation with decreased immunoreactive protein levels of the NR2A/2B subunits, and an altered NMDA receptor functionality. Journal of Neurochemistry 69, 1983–1994.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Tae-Cheon Kang
  • In Koo Hwang
  • Seung-Kook Park
  • Sung-Jin An
  • Dae-Kun Yoon
  • Seung Myung Moon
  • Yoon-Bok Lee
  • Heon-Soo Sohn
  • Sa Sun Cho
  • Moo Ho Won

There are no affiliations available

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