Skip to main content
SpringerLink
Log in

Ornithine decarboxylase in reversible cerebral ischemia: an immunohistochemical study

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Anesthetized Mongolian gerbils were subjected to 5-min ischemia and 8 h of recirculation. Vibratiom sections were taken for studying changes in ornithine decarboxylase (ODC) immunoreactivity using an antiserum to ODC, and tissue samples were taken for measuring ODC activity. After 5-min ischemia and 8-h recirculation ODC activity increased 11.5-, 5.9-, and 7.9-fold in the cerebral cortex, striatum and hippocampus, respectively (P≤0.05 to 0.01). In the cortex, striatum and hippocampus of control animals immunoreactivity was low but clearly above the detection limit. The reaction was confined to neurons. After 5-min ischemia and 8-h recirculation a sharp increase in immunoreactivity was observed confined to neurons, indicating that the postischemic activation of polyamine metabolism is a neuronal response to ischemia. The immunoreactivity was markedly increased in the perinuclear cytoplasm and the dendrites. In the striatum the density of neurons exhibiting a sharp increase in immunoreactivity was more pronounced in the lateral than in the ventral part. In the hippocampus a strong reaction was present in all subfields but the CA1 subfield was particularly affected. The present study demonstrates for the first time that biosynthesis of a protein is markedly activated during the first 24 h of recirculation after 5-min cerebral ischemia of gerbils even in the vulnerable CA1 subfield, in which the overall protein synthesis is sharply reduced at the same time. Studying polyamine metabolism after ischemia may, thus, provide new information about the basic molecular mechanisms responsible for the altered gene expression after metabolic stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bodsch W, Takahashi K, Barbier A, et al, (1985) Cerebral protein synthesis and ischemia. Prog Brain Res 63:197–210

    Google Scholar 

  2. Bondy SC, Walker CH, (1986) Polyamines contribute to calcium-stimulated release of aspartate from brain particulate fraction. Brain Res 371:96–100

    Google Scholar 

  3. Dienel GA, Cruz NF (1984) Induction of brain ornithine decarboxylase during recovery from metabolic, mechanical, thermal, or chemical injury. J Neurochem 42:1053–1061

    Google Scholar 

  4. Dienel GA, Cruz NF, Rosenfeld SJ (1985) Temporal profiles of proteins responsive to transient ischemia. J Neurochem 44:600–610

    Google Scholar 

  5. DeLeo J, Toth L, Schubert P, Rudolphi K, Kreutzberg GW (1987) Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the mongolian gerbil and protection by propentofylline (HWA 285). J Cereb Blood Flow Metab 7:745–751

    Google Scholar 

  6. Dempsey RJ, Maley BE, Cowen D, Olson JW (1988) Ornithine decarboxylase and immunohistochemical location in postischemic brain. J Cereb Blood Flow Metab 8:843–847

    Google Scholar 

  7. Dempsey RJ, Carney JM, Kindy MS (1991) Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. J Cereb Blood Flow Metab (in press)

  8. Dorn A, Müller M, Bernstein H-G, Pajunen A, Järvinen M (1987) Immunohistochemical localization of l-ornithine decarboxylase in developing rat brain. Int J Dev Neurosci 5:145–150

    Google Scholar 

  9. Dornay M, Gilad VH, Shiler I, Gilad GM (1986) Early polyamine treatment accelearates regeneration of rat sympathetic neurons. Exp Neurol 92:665–674

    Google Scholar 

  10. Gilad GM, Gilad VH (1983) Polyamine biosynthesis is required for survival of sympathetic neurons after axonal injury. Brain Res 273:191–194

    Google Scholar 

  11. Gilad GM, Gilad VH (1991) Polymines can protect against ischemia-induced nerve cell death in gerbil forebrain. Exp Neurol 111:349–355

    Google Scholar 

  12. Goto K, Ishige A, Sekiguchi K, Iizuka S, Sugimoto A, Yuzurihara M, Aburada M, Hosoya E, Kogure K (1990) Effects of cycloheximide on delayed neuronal death in rat hippocampus. Brain Res 534:299–302

    Google Scholar 

  13. Graham RC, Karnovsky MJ (1966) Glomerula permeability: Ultrastructural cytochemical studies using peroxidases as protein tracers. J Exp Med 124:1123–1134

    Google Scholar 

  14. Heby O (1981) Role of polyamines in the control of cell proliferation and differentiation. Differentiation 19:1–20

    Google Scholar 

  15. Iqbal Z, Koenig NH (1985) Polyamines appear to be second messengers in mediating Ca2+ fluxes and neurotransmitter release in potassium-stimulated synaptosomes. Biochem Biophys Res Commum 133:563–573

    Google Scholar 

  16. Isomaa VV, Pajunen AEI, Bardin CW, Jänne DA (1983) Ornithine decarboxylase in mouse kidney. Purification, characterization, and radioimmunological determination of the enzyme protein. J Biol Chem 258:6735–6740

    Google Scholar 

  17. Jørgensen MB, Deckert J, Wright DC, Gehlert DR (1989) Delayed c-fos proto-oncogene expression in the rat hippocampus induced by transient global ischemia: an in situ hybridization study. Brain Res 484:393–398

    Google Scholar 

  18. Kiessling M, Auer NR, Kleihues P, Siesjö BK (1986) Cerebral protein synthesis during long-term recovery from severe hypoglycemia J Cereb Blood Flow Metab 6:42–51

    Google Scholar 

  19. Kleihues P, Hossmann K-A, Pegg AE, Kobayashi K, Zimmermann V (1975) Resusciation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. Brain Res 95:61–73

    Google Scholar 

  20. Koenig H, Goldstone AD, Lu CY (1983) Blood-brain barrier breakdown in brain edema following cold injury is mediated by microvascular polyamines. Biochem Biophys Res Commun 116:1036–1048

    Google Scholar 

  21. Koenig H, Goldstone AD, Lu CY (1989) Blood-brain barrier breakdown in cold-injured brain is linked to a biphasic stimulation of ornithine decarboxylase activity and polyamine synthesis: both are coordinately inhibited by verapamil, dexamethasone, and aspirin. J Neurochem 52:101–109

    Google Scholar 

  22. Komulainen H, Bondy SC (1987) Transient elevation of intrasynaptosomal free calcium by putrescine. Brain Res 401:50–54

    Google Scholar 

  23. Laitinen PH, Huhtinen R-L, Hietala OA, Pajunen AEI (1986) Ornithine decarboxylase activity in brain regulated by a specific macromolecule, the antizyme. J Neurochem 44:1885–1891

    Google Scholar 

  24. Markwell MA, Berger SP, Paul SM (1990) The polyamine synthesis inhibitor α-difluoromethylornithine blocks NMDA-induced neurotoxicity. Eur J Pharmacol 1990; 182:607–609

    Google Scholar 

  25. Paschen W, Schmidt-Kastner R, Djuricic B, Meese C, Linn F, Hossmann K-A (1987) Polyamine changes in reversible cerebral ischemia J Neurochem 49:35–37

    Google Scholar 

  26. Paschen W, Hallmayer J, Röhn G (1988) Regional changes of polyamine profiles after reversible cerebral ischemia in mongolian gerbils: effects of nimodipine and barbiturate. Neurochem Pathol 8:27–41

    Google Scholar 

  27. Paschen W, Röhn G, Meese CO, Djuricic B, Schmidt-Kastner R (1988) Polyamine metabolism in reversible cerebral ischemia: effect of α-difluoromethylornithine. Brain Res 453:9–16

    Google Scholar 

  28. Paschen W, Hallmayer J, Mies G, Röhn G (1990) Ornithine decarboxylase activity and putrescine levels in reversible cerebral ischemia of Mongolian gerbils: effect of barbiturate. J Cereb Blood Flow Metab 10:236–242

    Google Scholar 

  29. Pegg AE, Lockwood DH, Williams-Ashman HG (1970) Concentration of putrescine and polyamines and their enzymatic synthesis during androgen-induced prostatic growth. Biochem J 117:17–31

    Google Scholar 

  30. Petito CK, Babiak T (1982) Early proliferative changes in astrozytes in postischemic noninfarcted rat brain. Ann Neurol 11:510–518

    Google Scholar 

  31. Reed CJ, de Belleroche J (1990) Induction of ornithine decarboxylase in cerebral cortex by excitotoxin lesion of nucleus basalis: association of postsynaptic responsiveness and N-methyl-d-aspartate activation. J Neurochem 55:780–787

    Google Scholar 

  32. Röhn G, Kocher M, Oschlies U, Hossmann K-A, Paschen W (1990) Putrescine content and structural defects in isolated fractions of rat brain after reversible cerebral ischemia. Exp Neurol 107:249–255

    Google Scholar 

  33. Thilmann R, Xie Y, Kleihues P, Kiessling M (1986) Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus. Acta Neuropathol (Berl) 71:88–93

    Google Scholar 

  34. Trout JJ, Koenig H, Goldstone AD, Lu CY (1986) Blood-brain barrier breakdown by cold injury. Lab Invest 55:622–631

    Google Scholar 

  35. Vass K, Welch WJ, Novak TS Jr (1988) Localization of 70-kDa stress protein induction in gerbil brain after ischemia. Acta Neuropathol 77:128–135

    Google Scholar 

  36. Wood H, de Belleroche J (1990) Induction of ornithine decarboxylase mRNA in cerebral cortex in response to kainate lesions of nucleus basalis: involvement of NMDA receptors. Neurosci Lett 111:176–182

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Neuromorphologie, Institut für Neurobiologie und Hirnforschung, Magdeburg, Federal Republic of Germany

    M. Müller & H. -G. Bernstein

  2. Abteilung für experimentelle Neurologie, Max-Planck-Institut für neurologische Forschung, Köln, Federal Republic of Germany

    M. Cleef, G. Röhn, P. Bonnekoh & W. Paschen

  3. Department of Biochemistry and Biocenter, University of Oulu, Oulu, Finland

    A. E. I. Pajunen

Authors
  1. M. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Cleef
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Röhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Bonnekoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. E. I. Pajunen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. -G. Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W. Paschen
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the Deutsche Forschungsgemeinschaft, Grant Pa 266/3-2, and by grants provided by the National Research Council for Natural Sciences, Academy of Finland and the Cancer Society of Finland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, M., Cleef, M., Röhn, G. et al. Ornithine decarboxylase in reversible cerebral ischemia: an immunohistochemical study. Acta Neuropathol 83, 39–45 (1991). https://doi.org/10.1007/BF00294428

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00294428

Key words

Search

Navigation