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Quinolinate-like neurotoxicity produced by aminooxyacetic acid in rat striatum

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Summary

The endogenous tryptophan metabolite quinolinic acid elicits in rodent brain a pattern of neuronal degeneration which resembles that caused by L-glutamate. Its qualities as a neurotoxic agent raised the hypothesis that quinolinic acid might be involved in the pathogenesis of human neurodegenerative disorders. Kynurenic acid, another endogenous tryptophan metabolite and preferential N-methyl-D-aspartate (NMDA) antagonist, has been shown to block quinolinic acid neurotoxicity. Here we report that microinjections of aminooxyacetic acid (AOAA), an inhibitor of kynurenine transaminase and of other pyridoxal phosphate-dependent enzymes, into the rat striatum produce neuronal damage resembling that caused by quinolinic acid. AOAA-induced striatal lesions can be prevented by kynurenic acid and the selective NMDA antagonist 2-amino-7-phosphonoheptanoic acid. These results suggest that AOAA produces excitotoxic lesions by depleting brain concentrations of kynurenic acid (inhibition of synthetic enzyme) or due to impairment of intracellular energy metabolism (depletion of cell energy resources). The concept of deficient neuroprotection due to metabolic defects might help to clarify the pathogenesis of human neurodegenerative disorders and to develop strategies that may be useful in their treatment.

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References

  1. Olney JW, Ho OL (1970) Nature (London) 227: 609–610

    Google Scholar 

  2. Olney JW, Ho OL, Rhee V (1971) Exp Brain Res 14: 61–76

    Google Scholar 

  3. Coyle JT, Schwarcz R (1976) Nature (London) 263: 244–246

    Google Scholar 

  4. McGeer EG McGeer PL (1976) Nature (London) 263: 517–519

    Google Scholar 

  5. Coyle JT, Schwarcz R, Bennet JP, Campochiaro P (1977) Prog Neuropsychopharmacol 1: 13–30

    Google Scholar 

  6. Schwarcz R, Foster AC, French ED, Whetsell WO, Köhler C (1984) Life Sci 35: 19–32

    Google Scholar 

  7. Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Brain Res 451: 205–212

    Google Scholar 

  8. Henderson LM, Hirsch HM (1949) J Biol Chem 181: 667–675

    Google Scholar 

  9. Schwarcz R, Whetsell WO, Mangano RM (1983) Science 219: 316–318

    Google Scholar 

  10. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986) Nature (London) 321: 168–171

    Google Scholar 

  11. Stone TW, Connick JH, Winn P, Hastings MH, English M (1987) In: Bock G, O'Connor M (eds) Selective neuronal death. CIBA Foundation Symp., vol 126. John Wiley, Chichester, pp 204–220

    Google Scholar 

  12. Schwarcz R, Whetsell WO, Turski WA (1988) In: Nappi G, Hornykiewicz O, Fariello RG, Agnoli A, Klawans H (eds) Neurodegenerative disorders: the role played by endotoxins and xenobiotics. Raven Press, New York, pp 7–21

    Google Scholar 

  13. Späth E (1921) Monatsh Chem 42: 89–95

    Google Scholar 

  14. Perkins MN, Stone TW (1982) Brain Res 247: 183–187

    Google Scholar 

  15. Foster AC, Vezzani A, French ED, Schwarcz R (1984) Neurosci Lett 48: 273–278

    Google Scholar 

  16. Ganong AH, Lanthorn TH, Cotman CW (1983) Brain Res 273: 170–174

    Google Scholar 

  17. Herrling PL (1985) Neuroscience 14: 417–426

    Google Scholar 

  18. Schwarcz R, Shoulson I (1987) In: Coyle JT (ed) Animal models of dementia: synaptic neurochemical perspective. Alan Liss, New York, pp 39–68

    Google Scholar 

  19. Schwarcz R, Speciale C, Turski WA (1989) In: Calne DB (ed) Parkinsonism and aging. Raven Press, New York, pp 97–105

    Google Scholar 

  20. Nakamura M, Turski WA, Whetsell WO, Schwarcz R (1987) Soc Neurosci Abstr 13: 1488

    Google Scholar 

  21. Turski WA, Nakamura M, Todd WP, Carpenter BK, Whetsell WO, Schwarcz R (1988) Brain Res 454: 164–169

    Google Scholar 

  22. Turski WA, Gramsbergen JBP, Traitler H, Schwarcz R (1989) J Neurochem 52: 1629–1636

    Google Scholar 

  23. Zeevalk GD, Nicklas WJ (1990) J Pharmacol Exp Ther 253: 1285–1292

    Google Scholar 

  24. Turski L, Bressler K, Rettig K-J, Löschmann P-A, Wachtel H (1991) Nature (London) 349: 414–418

    Google Scholar 

  25. Schapira AHV, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD (1990) J Neurochem 55: 2142–2145

    Google Scholar 

  26. DaVanzo JP, Matthews RJ, Stafford JE (1964) Toxicol Appl Pharmacol 6: 388–395

    Google Scholar 

  27. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  28. Fink RP, Heimer L (1967) Brain Res 4: 369–374

    Google Scholar 

  29. Lowe IP, Robins E, Eyerman GS (1958) J Neurochem 3: 8–18

    Google Scholar 

  30. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) J Biol Chem 193: 265–275

    Google Scholar 

  31. Markwell MAK, Haas SM, Bieber LL, Starr NE (1978) Anal Biochem 87: 206–210

    Google Scholar 

  32. McDonald JW, Silverstein FS, Johnston MV (1988) Brain Res 459: 200–203

    Google Scholar 

  33. Ikonomidou C, Mosinger JL, Shahid Salles K, Labruyere J, Olney JW (1989) J Neurosci 9: 2809–2818

    Google Scholar 

  34. Olney JW, Price MT, Samson L, Labruyere J (1986) Neurosci Lett 65: 65–71

    Google Scholar 

  35. Parker WD, Boyson SJ, Luder AS, Parks JK (1990) Neurology 40: 1231–1234

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Medical School, Jaczewskiego 8, PL-20-090, Lublin, Poland

    W. A. Turski, E. Urbańska, M. Sieklucka & C. Ikonomidou

Authors
  1. W. A. Turski
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  2. E. Urbańska
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  3. M. Sieklucka
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  4. C. Ikonomidou
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Additional information

This work was supported by research grant from the Polish Academy of Sciences.

These data have been communicated to the International Congress on Amino Acid Research held in Vienna in August 7–12, 1989.

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Turski, W.A., Urbańska, E., Sieklucka, M. et al. Quinolinate-like neurotoxicity produced by aminooxyacetic acid in rat striatum. Amino Acids 2, 245–253 (1992). https://doi.org/10.1007/BF00805946

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  • DOI: https://doi.org/10.1007/BF00805946

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