Advertisement

Progressive Neurodegeneration of the Dopaminergic system and Inhibition of the Complex I Induced by the Chloral-Derived Tetrahydro-β-Carboline TaClo

  • K.-H. Sontag
  • C. Heim
  • T. A. Sontag
  • W. Kolasiewicz
  • W. Clement
  • C. Grote
  • W. Wesemann
  • B. Janetzky
  • H. Reichmann
  • D. Feineis
  • R. God
  • G. Bringmann
  • D. Rausch
  • M. Abdel-mohsen
  • M. Abdel-moneim
  • W. W. Chan
  • E. Koutsilieri
  • B. Zielke
  • M. Götz
  • W. Gsell
  • P. Riederer
Part of the Advances in Behavioral Biology book series (ABBI, volume 47)

Abstract

TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) appears to be a neurotoxic drug able to induce a slow developing degeneration of dopamine neurons. This is indicated from measurements of the apomorphine-induced locomotor activity. These experiments were carried out on rats in an open field system several days and 9 months after the end of a period of a 7 week injection of 0.2mg/ kg TaClo i. p. The neurotoxic potency appears to be different from that of MPTP or MPP+. MPP+ produces symptoms in monkeys that very closely resemble those in humans suffering from Parkinson’s disease (PD), but severe symptoms develop very rapidly after administration of the toxic drug. The use of the drug MPP+, therefore, does not allow the study of the different stages of the slowly progressive illness of PD in man, as the time between injection of drug and symptoms is to rapid (see also Jenner et al., 1986; Mohanakumar et al., 1994). It is therefore desirable to develop animal models that mimic the slow progressive advance of PD with the late onset of the first typical symptoms. We are not aware that such a model exists.

Keywords

Locomotor Activity Dopaminergic System Concentration Of700 Injection Period Intact Mitochondrion 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beninger, R.J., 1983, The role of dopamine in locomotor activity and learning, Brain Res. Rev. 173-196Google Scholar
  2. Berger, B., di Porzio, U., Daguet, M.C., Gay, M., Vigny, A., Glowinski, J., Prochiantz, A., 1982, Longterm development of mesencephalic dopasminergic neurons of mouse embryos in dissociated primary cultures: morhological and histochemical characteristics, Neurosci.Lett. 7:193–205CrossRefGoogle Scholar
  3. Bottenstein, J.E., Sato, G.H., 1979, Growth of a rat neoblastoma cell line in serum free supplemented medium. Proc.Natl.Acad.Sci. U.S.A., 76:514–517PubMedCrossRefGoogle Scholar
  4. Bringmann, G., Hille, A., 1990, 1-trichlormethyl-1,2,3,4-tetra-hydro-β-carboline-a potential chloral-derived indole alkaloid in man, Arch.Pharm. 323: 567–569CrossRefGoogle Scholar
  5. Bringmann, G., Feineis, D., Friedrich, H., Hille, A., 1991, Endogenous alkaloids in man-synthesis, analytics, in vivo identification, and medical importance, Planta Med. 57 (Suppl. 1): 73–84CrossRefGoogle Scholar
  6. Bringmann, G., Friedrich, H. Feineis, D., 1992, Trichloroharmanes as potential endogenously formed inducers of Morbus Parkinson: synthesis, analysis, and first in vivo investigations, J. Neural Transm (Suppl.) 38: 15–26Google Scholar
  7. Bringmann, G., God, R., Feineis, D., Wesemann, W., Riederer, P., Rausch, W.D., Reichmann, H., Sontag, K.-H., 1995a, The TaClo concept: 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo), a new toxin for dopaminergic neurons, J. Neural Transm., in pressGoogle Scholar
  8. Bringmann, G., God, R., Feineis, D., Janetzky, B., Reichmann, H., 1995b, TaClo as a neurotoxic lead: improved synthesis, stereochemical analysis, and inhibition of the mitochondrial respiration chain, J. Neural Transm., in pressGoogle Scholar
  9. Bringmann, G., Feineis, D., God, R., Fähr, S., Wesemann, W., Clement, H.-W., Grote, C. Sontag, K.-H., Heim, C., Sontag, T., Kolasiewicz, W., Reichmann, H., Janbetzky, B., Rausch, W-D., Abdel-Mohsen, M., Koutsilieri, E., Zielke, B., Riederer, P., 1995c, Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid: in vivo and in vitro studies, Biogenic Amines, in pressGoogle Scholar
  10. Bruckner, J.V., Davis, B.D. Blancato, J.N., 1989, Metabolism, toxicity, and carcinogenicity of trichloroethylene, Crt.Rev.Toxicol. 20: 31–50CrossRefGoogle Scholar
  11. Cespuglio, R., Faradji, H., Buda, M., Ganon, F., Pujol, J.F., 1981, Differential pulse voltammetry in brain tissue 2. Detections of 5-hydroxyin-dolacetic acid in the rat striatum, Brain Res 223: 299–311PubMedCrossRefGoogle Scholar
  12. Fink, J.S., and Smith, G.P., 1980, Mesolimbiccortical dopamine terminal fields are necessary for normal locomotor and investiga-tory exploration in rats, Brain Res. 199: 359–384PubMedCrossRefGoogle Scholar
  13. Gonon, F., Buda, M., Cespuglio, R., Jouvet, M., Pujol, J.F., 1980, In vivo electrochemical detection of catechols in the neostriatum of anaesthetized rats: dopamine or DOPAC?, Nature 286: 902–904PubMedCrossRefGoogle Scholar
  14. Grote, C., Clement, H.-W., Wesemann, W., Bringmann, G., Feineis, D., Riederer, P., Sontag, K.-H., 1995, Biochemical lesions ofthe nigrostriatal system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) and derivates, J. Neural Transm., in pressGoogle Scholar
  15. Jenner, P., Marsden, C.D., Costali, B., Naylor, R.J., 1986, MPTP and MPP+ induced neurotoxicity in rodents and the common marmor-sets as experimental model for investigating Parkinson’s disease. In: S.P. Markey, N. Jr. Castagnoli, A.J. Trevor, I.J. Kopin, (eds.), MPTP: a neurotoxin producing a Parkinsonian syndrome, Academic Press, Orlando San Diego New York, pp 45–68Google Scholar
  16. Janetzky, B., God, R., Bringmann, G., Reichmann, H., 1995, 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline, a new inhibitor of complex I, J. Neural Transm., in pressGoogle Scholar
  17. King, T.E., 1967, Preparation of succinate-cytochrome reductase and the cytochrome b-c, particle, and reconstitution of succinate-cytochrome c reductase, Methods Enzymol. 10, 216–225CrossRefGoogle Scholar
  18. Koob, G.F., Stinus, L., and LeMoal M., 1981, Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system, Behav.Brain Res., 3: 341–359PubMedCrossRefGoogle Scholar
  19. Mohanakumar, K.P., de Bartolomeis, A., Wu, R.M., Yeh, K.J., Sternberger, L.M. Peng, S.Y, Murphy, D.L., Chiuh, C.C., 1994, Ferrous-citrate complex and nigral degeneration: Evidence for free radical formation and lipid peroxidation, Ann NY Acad Sci 738:392–399PubMedCrossRefGoogle Scholar
  20. O’Neill, R.D., Fillenz, M., 1985, Simultaneous monitoring of dopamine release in rat frontal cortex, nucleus accumbens and striatum: effect of drugs, circadian changes and correlations with motor activity, Neuroscience 16: 49–55PubMedCrossRefGoogle Scholar
  21. Paxinos, A., Watson, C., 1982, The rat brain in stereotaxic coordinates, Academic Press, SidneyGoogle Scholar
  22. Ponchon, J.L., Cespuglio, R., Ganon, F., Jouvet, M., Pujol, J.F., 1979, Normal pulse polarography with carbon fibre electrodes for in vitro and in vivo determination of catecholamines, Anal.Chem. 51: 1483–1486PubMedCrossRefGoogle Scholar
  23. Ragan, C.I., Wilson, M.T., Darley-Usmar, V.M., Lowe, P.N., 1987, Sub-fractionation of mitochondria and isolation of the proteins of oxidative phosphorylation. In: Mitochondria, a practical approach, V.M. Darley-Usmar, D. Rickwood and M.T. Wilson (Edts.). IRL Press, Oxford, Washington DC, pp. 79–112Google Scholar
  24. Rausch, W.-D., Abdel-mohsen, M., Koutsilieri, E., Chan, W.W., Bringmann, G., 1995, Studies of the potentially endogenous toxin TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) in neural and glia cell cultures, J. Neural Transm., in pressGoogle Scholar
  25. Reichmann, H., Hoppeler, H., Matthieu-Costello, O., von Berger, F., Pette, D., 1985, Biochemical and ultrastructural changes of skele-tal muscle mitochondria after chronic electrical stimulation in rabbits, Pflügers Arch. 404, 1–9PubMedCrossRefGoogle Scholar
  26. Rickwood, D., Wilson, M.T., Darley-Usmar, V.M., 1987, Isolation and characteristics of intact mitochondria. In: Mitochondria, a practical approach, V.M. Darley-Usmar, D. Rickwood and M.T. Wilson (Edts.). IRL Press, Oxford, Washington DC, pp. 1–16Google Scholar
  27. Robinson, J.B., Brent, L.G., Sumegi, B., Srere, P.A., 1987, An enzymatic approach to the study of the Krebs tricarboxylic acid cycle. In: Mitochondria, a practical approach, V.M. Darley-Usmar, D. Rickwood, M.T. Wilson (Edts.), IRL Press, Oxford, Washington DC, pp. 153–170Google Scholar
  28. Romijin, H.J., Habets, A.M.C., Mud, M.T. Wolters, P.S., 1982, Nerve outgrowth, synaptogenesis and bioelectric activity in fetal rat cerebral cortex tissue cultured in serum-free, chemically defined medium, Dev.Brain.Res. 2:583–589CrossRefGoogle Scholar
  29. Rose, I.A., O’Conell, E.L., 1967, Mechanism of aconitase action. I. The hydrogen transfer reaction. J.Biol.Chem. 242:1870–1879PubMedGoogle Scholar
  30. Sofic, E., 1986, Untersuchungen von biogenen Aminen, Metallen, Ascorbinsäure und Gluthadion mittels HPLC-ECD und deren Verhalten in ausgewählten Lebensmitteln und im Organismus von Tier und Mensch. Thesis, Technical University ViennaGoogle Scholar
  31. Sottacasa, G., Kuylenstierna, B., Ernster, L., Bergstrand, A., 1967, An electron transport system assoziated with the outer membrane of the mitochondria, J.Cell.Biol. 32:415–438CrossRefGoogle Scholar
  32. Wharton, D.C., Tzagoloff, A., 1967, Cytochrome oxidase from beef heart mitochondria. Methods Enzymol. 10:245–250CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • K.-H. Sontag
    • 1
  • C. Heim
    • 1
  • T. A. Sontag
    • 1
  • W. Kolasiewicz
    • 2
  • W. Clement
    • 3
  • C. Grote
    • 3
  • W. Wesemann
    • 3
  • B. Janetzky
    • 4
  • H. Reichmann
    • 4
  • D. Feineis
    • 5
  • R. God
    • 5
  • G. Bringmann
    • 5
  • D. Rausch
    • 6
  • M. Abdel-mohsen
    • 6
  • M. Abdel-moneim
    • 6
  • W. W. Chan
    • 6
  • E. Koutsilieri
    • 7
  • B. Zielke
    • 7
  • M. Götz
    • 7
  • W. Gsell
    • 7
  • P. Riederer
    • 7
  1. 1.Max-Planck-Institut for Experimental MedicineGöttingenGermany
  2. 2.Institute of PharmacologyPolish Academy of SciencesKrakovPoland
  3. 3.Institute of Physiological Chemistry, Department of NeurochemistryUniversity of MarburgMarburgGermany
  4. 4.University Hospital of NeurologieUniversity of WürzburgWürzburgGermany
  5. 5.Institute of Organic ChemistryUniversity of WürzburgGermany
  6. 6.Institute of Medical ChemistryUniversity of Veterinary MedicineViennaAustria
  7. 7.Clinical Neurochemistry, Department of PsychiatryUniversity of WürzburgWürzburgGermany

Personalised recommendations