Advertisement

Neurochemical Research

, Volume 17, Issue 9, pp 835–839 | Cite as

Effect of 2,5-hexanedione and 3,4-dimethyl-2,5-hexanedione on retrograde axonal transport in sciatic nerve

  • Mohammad I. Sabri
Original Articles

Abstract

The effects of systemically introduced neurotoxic solvents 2,5-hexanedione (2,5-HD) and 3,4-dimethyl-2,5-hexanedione (DMHD) on retrograde axonal transport (RT) of125I-labeled tetanus toxin (TT) was studied in rat and mouse sciatic nerves. The rate of retrograde transport of TT in control rat sciatic nerves was slightly higher (6.8±0.4 mm/h) than in mouse sciatic nerves (5.4±0.5 mm/h). A single high dose of 2,5-HD (1,000 mg/kg, i.p.) produced a time-dependent effect on RT in mouse sciatic nerves. 2,5-HD caused a gradual decrease in the velocity of RT (approximately 65% inhibition between 2.0–2.5 h) with a reversal to normal rate 3–5 h after the toxin administration. The effect of DMHD on RT was examined following semi-chronic treatment in rats. DMHD caused a significant decrease (approximately 50%) in the rate of TT transport, in addition, it produced weight loss and hind-limb paralysis.

Key Words

2,5-Hexanedione 3,4-dimethyl-2,5-hexanedione axonal transport, retrograde axonal transport neurotoxicity neuropathy peripheral nerves 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Anthony, D. C., Amarnath, V., and Graham, D. G. 1990. Pyrrole-mediated protein crosslinking: toward an understanding of the molecular mechanism. The Toxicologist 10:183 (abs).Google Scholar
  2. 2.
    Anthony, D. C., Boekelheide, K., and Graham, D. G. 1983. The effect of 3,4-dimethyl substitution on the neurotoxicity of 2,5-hexanedione. I. Accelerated clinical neuropathy is accompanied by more proximal axonal swellings. Toxicol. Appl. Pharm. 71:362–371.Google Scholar
  3. 3.
    Boekelheide, K. 1987. 2,5-Hexanedione alters microtubule assembly: II. Enhanced polymerization of crosslinked tubulin. Toxicol. Appl. Pharmacol. 88:383–396.Google Scholar
  4. 4.
    Boekelheide, K. 1988. Rat testis during 2,5-hexanedione intoxication and recovery. II. Dynamics of pyrrole reactivity, tubulin content, and microtubule assembly. Toxicol. Appl. Pharmacol. 92:28–33.Google Scholar
  5. 5.
    Braengaard, H., and Sidenius, P. 1986. Anterograde components of axonal transport in motor and sensory nerves in experimental 2,5-hexanedione neuropathy. J. Neurochem. 47:31–37.Google Scholar
  6. 6.
    Braengaard, H., and Sidenius, P. 1986. The retrograde fast component of axonal transport in motor and sensory nerves of the rat during administration of 2,5-hexanedione. Brain Res. 378:1–7.Google Scholar
  7. 7.
    Couri, D., and Nachtman, J. P. 1979. Biochemical and biophysical studies of 2,5-hexanedione neuropathy. Neurotoxicology 1:269–283.Google Scholar
  8. 8.
    DeCaprio, A. P. 1985. Molecular mechanisms of diketone neurotoxicity. Chem. Biol. Interactions 54:257–270.Google Scholar
  9. 9.
    Gillies, P. J., Norton, R. M., White, E. L., and Bus, J. S. 1980. Inhibition of sciatic nerve sterologenesis in hexacarbon induced distal axonopathy in the rat. Toxicol. Appl. Pharmacol. 54:217–222.Google Scholar
  10. 10.
    Gillies, P. J., Norton, R. M., and Bus, J. S. 1981. Inhibition of sterologenesis but glycolysis in 2,5-hexanedione-induced distal axonopathy in the rat. Toxicol. Appl. Pharmacol. 59:287–292.Google Scholar
  11. 11.
    Graham, D. G., Szakal-Quin, G., Priest, J. W., and Anthony, D. C. 1984. In vitro evidence that covalent crosslinking of neurofilaments occurs in gamma-diketone neuropathy. Proc. Natl. Acad. Sci. USA. 81:4979–4982.Google Scholar
  12. 12.
    Griffin, J. W., Fahnestock, K. E., Price, D. L., and Cork, L. C. 1983. Cytoskeletal disorganization induced by local application of beta, beta'-Iminodipropiononitrile and 2,5-hexanedione. Ann. Neurol. 14:55–61.Google Scholar
  13. 13.
    Griffin, J. W., Anthony, D. C., Fahnestock, K. E., Hoffman, P. N., and Graham, D. G. 1984. 3,4-Dimethyl-2,5-hexanedione impair the axonal transport of neurofilament protein. J. Neurosci. 4:1516–1526.Google Scholar
  14. 14.
    Howland, R. D., Vyas, I. L., Lowndes, H. E., and Argentieri, T. M. 1980. The etiology of toxic peripheral neuropathies: in vitro effect of acrylamide and 2,5-hexanedione on brain enolase and other glycolytic enzymes. Brain Res. 202:131–142.Google Scholar
  15. 15.
    Lapadula, D. M., Irwin, R. D., Suwita, E., and Abou-Donia, M. B. 1986. Cross-linking of neurofilament proteins of rat spinal cord in vivo after administration of 2,5-hexanedione. J. Neurochem. 46:1843–1850.Google Scholar
  16. 16.
    Medrano, C. J., and Lopachin, R. M. 1989. Effects of acrylamide and 2,5-hexanedione on brain mitochondrial respiration. Neurotoxicology, 10:249–256.Google Scholar
  17. 17.
    Monaco, S., Simonati, A., Rizzuto, N., Autilio-Gambetti, L., and Gambetti, P. 1988. Hexacarbon axonopathy: the morphological expression of altered cytoskeletal translocation. Pages 239–251,in G. Nappi, O. Hornykiewicz, R. G. Fariello, A. Agnoli, and H. Klawans, (eds.), Neurodegenerative Disorders: The Role Played by Endotoxins and Xenobiotics Raven Press, NY.Google Scholar
  18. 18.
    Monaco, S., Autilio-Gambetti, L., Zabel, D., and Gambetti, P. 1985. Giant axonal neuropathy: Acceleration of neurofilament transport in optic axons. Proc. Natl. Acad. Sci. USA. 82:920–924.Google Scholar
  19. 19.
    Monaco, Jacob, J., Jenich, H., Patton, A., Autilio-Gambetti, L., and Gambetti, P. 1989. Axonal transport of neurofilament is accelerated in peripheral nerve during 2,5-hexanedione intoxication. Brain Res. 491:328–334.Google Scholar
  20. 20.
    Moretto, A., and Sabri, M. I. 1988. Progressive deficits in retrograde axon transport precede degeneration of motor axons in acrylamide neuropathy. Brain Res. 440:18–24.Google Scholar
  21. 21.
    Planas, A. M., and Cunningham, V. J. 1987. Uncoupling of cerebral glucose supply and utilization after hexane-2,5-dione intoxication in the rat. J. Neurochem. 48:816–823.Google Scholar
  22. 22.
    Sabri, M. I., Moore, C. L., and Spencer, P. S. 1979. Studies on the biochemical basis of distal axonopathies. I. Inhibition of glycolysis by neurotoxic hexacarbon compounds. J. Neurochem. 32:683–689.Google Scholar
  23. 23.
    Sabri, M. I., Ederle, K., Holdsworth, C. E., and Spencer, P. S. 1979. Studies on the biochemical basis of distal axonopathies. II. Specific inhibition of fructose-6-P-kinase by 2,5-hexanedione and methyl-n-butyl ketone. Neurotoxicology, 1:285–297.Google Scholar
  24. 24.
    Sabri, M. I., and Spencer, P. S. 1987. Retrograde axon transport inhibition by 2,5-hexanedione in mouse sciatic nerve. J. Neurochem. 48:S55.Google Scholar
  25. 25.
    Sabri, M. I., and Spencer, P. S. 1989. Inhibition of retrograde axonal transport by 3,4-dimethyl-2,5-hexanedione. Soc. Neurosc. Abs. 15:687.Google Scholar
  26. 26.
    Sahenk, Z., and Mendell, J. R. 1981. Acrylamide and 2,5-hexanedione neuropathies: Abnormal bidirectional transport rate in distal axons. Brain Res. 219:397–405.Google Scholar
  27. 27.
    Sayre, L. A., Autilio-Gambetti, L., and Gambetti, P. 1985. Pathogenesis of experimental giant neurofilamentous axonopathies: A unified hypothesis based on chemical modification of neurofilaments. Brain Res. Rev. 10:69–83.Google Scholar
  28. 28.
    Sickles, D. W. 1989. Toxic neurofilamentous axonopathies and fast anterograde axonal transport. II. The effects of single doses of neurotoxic and non-neurotoxic diketones and beta,beta'-iminodipropionitrile (IDPN) on the rate and capacity of transport. Neurotoxicology. 10:103–112.Google Scholar
  29. 29.
    Spencer, P. S., and Griffin, J. W. 1982. Disruption of axoplasmic transport by neurotoxic agents. The 2,5-hexanedione model. Pages 92–103,in D. G. Weiss, and A. Gorio, (eds.), Axoplasmic Transport in Physiology and Pathology, Springer-Verlag, Berlin.Google Scholar
  30. 30.
    Spencer, P. S., Schaumburg, H. H., Sabri, M. I., and Veronesi, B. 1980. The enlarging view of hexacarbon neurotoxicity. Pages 279–356,in L. Goldberg (ed.), Critical Reviews in Toxicology, CRC Press, Inc. Boca Raton.Google Scholar
  31. 31.
    Zagoren, J. C., Politis, M., and Spencer, P. S. 1983. Rapid reorganization of the axonal cytoskeleton induced by a gamma diketone. Brain Res. 270:162–164.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Mohammad I. Sabri
    • 1
  1. 1.Center For Research On Occupational And Environmental Toxicology (L606)Oregon Health Sciences University Portland

Personalised recommendations