Molecular and Chemical Neuropathology

, Volume 17, Issue 1, pp 79–89 | Cite as

Aluminum-induced acute cholinergic neurotoxicity in rat

  • Jeng-Hsiung F. Peng
  • Zhi-Chung Xu
  • Zhi-Xin Xu
  • Joseph C. Parker
  • Edward R. Friedlander
  • Jian-Ping Tang
  • Srikumaran Melethil
Original Articles

Abstract

In the present study the acute effect of intravenous aluminum chloride (1 mg/kg) on choline acetyltransferase (ChAT) and acetyl-cholinesterase (AChE) activities of rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB) as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min after femoral vein injection. Two hours following aluminum injection, ChAT activity in the basal forebrain and hippocampus was significantly reduced by 30% and 22%, respectively, whereas no change was observed in the caudate nuclei. On the other hand, AChE activity was significantly increased by 45% in the caudate nuclei, whereas little change was observed in other brain areas. This report demonstrates that rapid transport of Al across the BBB, and the acute nature of Al neurotoxicity in rats.

Index Entries

Aluminum transport blood-brain barrier cerebrospinal fluid aluminum acute aluminum effect cholinergic neurotoxicity neurofibrillary degeneration choline acetyltransferase acetylcholinesterase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alfrey A. C., LeGendre G. R., and Kaehny W. D. (1976) The dialysis encephalopathy syndrome: Possible aluminum intoxication.N. Engl. J. Med. 294, 184–188.PubMedGoogle Scholar
  2. Armstrong D. M., Bruce G., Hersh L. B., and Terry R. D. (1986) Choline acetyltransferase immunoreactivity in neuritic plaques of Alzheimer brain.Neurosci. Lett. 71, 229–234.PubMedCrossRefGoogle Scholar
  3. Boegman R. J., and Bates C. A. (1984) Neurotoxity of aluminum.Can. J. Physiol. Pharmacol. 62, 1010–1014.PubMedGoogle Scholar
  4. Candy J. M., Oakley A. E., Atack J., Perry R. H., Perry E. K., and Edwardson J. A. (1984) New observations on the nature of senile plaque cores, inDevelopments in Neuroscience, Vol. 17: Regulation of Transmitter Function: Basic and Clinical Aspects (Vizi E. S. and Magyar K., eds.), pp. 301–304, Elsevier, New York.Google Scholar
  5. Chafi A. H., Hauw J. J., Rancurel G., Berry J. J., and Galle C. (1991) Absence of alumunim in Alzheimer’s disease brain tissue: Electron microprobe and ion microprobe studies.Neurosci. Lett. 123, 61–64.PubMedCrossRefGoogle Scholar
  6. Crapper McLachlan D. R. and De Boni U. (1980) Aluminum in human brain disease-an overview.Neurotoxicology 1, 3–16.Google Scholar
  7. Crapper McLachlan D. R., Lukiw W. J., and Kruck T. P. A. (1989) New evidence for an active role of aluminum in Alzheimer’s disease.Can. J. Neuro. Sci. 16, 490–497.Google Scholar
  8. Davis P. and Maloney A. J. F. (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease.Lancet 2, 1403.CrossRefGoogle Scholar
  9. Davis P. and Wolozin B. L. (1987) Recent advances in the neurochemistry of Alzheimer’s disease.J. Clin. Psychiatry 48, 23–30.Google Scholar
  10. DeBoni U., Otvos A., Scott J. W., and Crapper McLachlan D. R. (1976) Neurofibrillary degeneration induced by systemic aluminum.Acta Neuropath. (Berl.)35, 285–294.Google Scholar
  11. Gulya K., Rackonczay Z., and Kasa P. (1990) Cholinotoxic effects of aluminum in rat brain.J. Neurochem. 54, 1020–1026.PubMedCrossRefGoogle Scholar
  12. Hetnarski B., Wisniewski H. M., Iqbal K., Dziedzic J. C., and Lajtha A. (1980) Central cholinergic activity in aluminum-induced neurofibrillary degeneration.Ann. Neurol. 7, 489–490.PubMedCrossRefGoogle Scholar
  13. Jacobs R. W., Duong T., Jones R. E., Trap G. A., and Scheibel A. B. (1989) A reexamination of aluminum in Alzheimer’s disease: Analysis by energy dispersive x-ray microprobe and flameless atomic absorption spectrophotometry.Can. J. Neurol. Sci. 16, 498–503.PubMedGoogle Scholar
  14. Johnson G. V. W. and Jope R. S. (1987) Aluminum alters cyclic AMP and cyclic GMP levels but not presynaptic cholinergic markers in rat brain in vitro.Brain Res. 403, 1–6.PubMedCrossRefGoogle Scholar
  15. Kitt C. A., Price D. L., Struble R. G., Cork L. C., Wainer B. H., Becker M. W., and Moble W. C. (1980) Evidence for cholinergic neuritis in senile plaques.Science 226, 1443–1445.CrossRefGoogle Scholar
  16. Kosik K. S., Bradley W. G., Goof P. F., Rasool C. G., and Selkoe D. J. (1983) Cholinergic function in lumbar aluminum myelopathy.J. Neuropath. Exp. Neurol. 42, 365–375.PubMedCrossRefGoogle Scholar
  17. Lai J. C. K., Lim L., and Davison A. N. (1981) Differences in the inhibitory effect of Ca2+, Mn2+, and Al3+ on the uptake of dopamine by synaptosomes from forebrain and straitum of the rat.Biochem. Pharmacol. 30, 3123–3125.PubMedCrossRefGoogle Scholar
  18. Lowry O. H., Rosebrough N. J., Farr N. J., and Randall R. J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  19. Markesbery W. R., Ehmann W. D., Hossain T. I. M., Alauddin M., and Goodin D. T. (1981) Instrumental neutron activation analysis of brain aluminum in Alzheimer disease and aging.Ann. Neurol. 10, 511–516.PubMedCrossRefGoogle Scholar
  20. Marquis J. K. (1982) Aluminum neurotoxicity: An experimental perspective.Bull. Environ. Contam. Toxicol. 29, 43–49.PubMedCrossRefGoogle Scholar
  21. McDermitt J. R., Smith A. L., Iqbal K., and Wisniewski H. M. (1979) Brain aluminum in aging and Alzheimer’s disease.Neurology 29, 809–814.Google Scholar
  22. Peng J. H., McGeer P. L., Kimura H., Sung, S. C., and McGeer E. G. (1980) Purification and immunochemical properties of choline acetyltransferase from human brain.Neurochem. Res. 5, 943–962.PubMedCrossRefGoogle Scholar
  23. Perl D. P. and Brody A. R. (1980) Alzheimer’s disease: X-ray spectrophotometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons.Science 208, 297–299.PubMedCrossRefGoogle Scholar
  24. Perl D. P. and Good P. F. (1990) Aluminum environment and Alzheimer’s disease: Active role or passive bystander?Neurobiol. Aging 11, 83.Google Scholar
  25. Roskams A. J. and Connor J. R. (1990) Aluminum access to the brain: A role for transferrin and its receptor.Proc. Natl. Acad. Sci. USA 87, 9024–9027.PubMedCrossRefGoogle Scholar
  26. Singer H. S., Searles C. D., Hahn I. H., March J. L., and Troncoso J. C. (1990) The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15).Brain Res. 528, 73–79.PubMedCrossRefGoogle Scholar
  27. Sung S. C. (1980) Acetylcholinesterase solubilized from normal and dystrophic muscles by collagenase treatment.Biochim. Biophys. Acta 628, 286–292.PubMedGoogle Scholar
  28. Wisniewski H. M., Moretz R. C., Sturman J. A., Wen G. Y., and Shek J. W. (1990) Aluminum toxicity in mammals.Environ. Geochem. Health 12, 115–130.CrossRefGoogle Scholar
  29. Xu Z. X., Pai S. M., and Melethil S. (1991) Kinetics of aluminum in the rat. II; dose-dependent urinary and biliary secretion.J. Pharmaceut. Sci. 80, 946–951.CrossRefGoogle Scholar
  30. Yates C. M., Simpson J., Russell D., and Gordon A. (1980) Cholinergic enzymes in neurofibrillary degeneration produced by aluminum.Brain Res. 197, 269–274.PubMedCrossRefGoogle Scholar
  31. Zubenko G. S. and Hanin I. (1989) Cholinergic and noradrenergic toxicity of intraventricular aluminum chloride in the rat hippocampus.Brain Res. 498, 381–384.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 1992

Authors and Affiliations

  • Jeng-Hsiung F. Peng
    • 1
  • Zhi-Chung Xu
    • 2
  • Zhi-Xin Xu
    • 2
  • Joseph C. Parker
    • 1
  • Edward R. Friedlander
    • 1
  • Jian-Ping Tang
    • 2
  • Srikumaran Melethil
    • 2
  1. 1.Department of Pathology, School of MedicineUniversity of Missouri-Kansas CityKansas CityUSA
  2. 2.School of PharmacyKansas CityUSA

Personalised recommendations