Skip to main content
SpringerLink
Log in

Neurotoxic effects of aluminium on embryonic chick brain cultures

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

Abstract

Toxic damage of brain cells by aluminium (A1) is discussed as a possible factor in the development of neurodegenerative disorders in humans. To investigate neurotoxic effects of A1, serum-free cultures of mechanically dissociated embryonic chick (stage 28–29) forebrain, brain stem and optic tectum, and for comparison meningeal cells, were treated with A1 (0–1000 μM) for 7 days. Effects of A1 on cell viability (lysosomal and mitochondrial activity) and differentiation (synthesis of cell-specific proteins) were found to the brain area specific with the highest sensitivity observed in optic tectum. No inhibiting effects on cell viability could be observed in cultures of forebrain and meninges in the concentration range tested. In all three brain tissue cultures, threshold levels for the reduction of cell differentiation parameters were found at lower concentrations [concentration resulting in a 50% decrease (IC50)>180 μM] than for the inhibitionof cell viability (IC50>280 μM) indicating a specific toxic potential of A1 for cytoskeletal alterations. The culture levels of nerve cellspecific markers microtubule-associated protein type 2 (the most sensitive parameter) and the 68-kDa neurofilament were inhibited at lower concentrations (IC50 180–630 μM) than the astrocyte-specific glial fibrillary acidic protein (IC50 700–∼1000 μM), demonstrating a particularly high sensitivity of neurons in comparison to astrocytes. Based on these differences in A1 sensitivity observed for different cell markers in the various brain tissue cultures, the in vitro system used in the present study proved to be a suitable model to assess brain area and cell type-specific neurotoxic effects of A1.

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. Alfrey AC (1983) Aluminum. Adv Clin Chem 23: 69–91

    Google Scholar 

  2. Atterwill CK, Davies WJ, Kyriakides MA (1990) an investigation of aluminium neurotoxicity using some in vitro systems. Alternat Lab Animals 18: 181–190

    Google Scholar 

  3. Barker FM (1992) Canthaxanthin and the eye, a critical ocular toxicological review. 1992 European meeting of the Toxicology Forum, Copenhagen (Denmark), June 1–5. CASET Ass Ltd, Fairfax (USA) pp 478–500

    Google Scholar 

  4. Bizzi A, Gambetti P (1986) Phosphorylation of neurofilaments is altered in aluminium intoxication. Acta Neuropathol (Berl) 71: 154–158

    Google Scholar 

  5. Bruinmk A (1992) Serum-free monolayer cultures of embryonic chick brain and retina: immunoassays of developmental markers, mathematical data analysis and establishment of optimal culture conditions. In: Zbinden G (ed) The brain in bits and pieces, M. T. C. Verlag,Zollikon, pp 23–50

    Google Scholar 

  6. Bruinink A, Birchler F (1993) Effects of cisplatin and ORG. 2766 in chick embryonic cell cultures. Arch Toxicol 67: 325–329

    Google Scholar 

  7. Bruinink A, Reiser P (1991) Ontogeny of MAP2 and GEAP antigens in primary cultures of embryonic chick brain. Effect of substratum, oxygen tension, serum and ARA-C. Int J Dev Neurosci 9: 269–279

    Google Scholar 

  8. Bruinink A, Zimmermann G, Riesen F (1991) Neurotoxic effects of chloroquine in vitro. Arch Toxicol 65: 480–484

    Google Scholar 

  9. Bruinink A, Reiser P, Müller M, Gähwiler BH, Zbinden G (1992) Neurotoxic effects of bismuth in vitro. Toxicol in Vitro 6: 285–293

    Google Scholar 

  10. Candy JM, Oakley AE, Mountfort SA, Taylor GA, Morris CM, Bishop HE, Edwardson JA (1992) The imaging and quantification of aluminium in the human brain using dynamic secondary ion mass spectrometry (SIMS). Biol Cell 74: 109–118

    Google Scholar 

  11. Cole GM, Wu K, Timiras PS (1985) A culture model for agerelated human neurofibrillary pathology. Int J Dev Neurosci 3: 23–32

    Google Scholar 

  12. Cork LC, Sternberger NH, Sternberger LA, Casanova MF, Struble RG, Price DL (1986) Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease. J. Neuropathol Exp Neurol 45: 56–64

    Google Scholar 

  13. Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science180: 511–513

    Google Scholar 

  14. Crapper DR, Krishnan SS, Quittkat S (1976) Aluminium, neurofibrillary degeneration and Alzheimer's disease. Brain 99: 67–80

    Google Scholar 

  15. Crapper McLachlan DR, Kruck TP, Lukiw WJ, Krishnan SS (1991) Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease? Can Med Assoc J 145: 793–804

    Google Scholar 

  16. DeBoni U, Otvos A, Scott JW, Crapper DR (1976) Neurofibrillary degeneration induced by systemic aluminum. Acta Neuropathol (Berl) 35: 285–294

    Google Scholar 

  17. Galle P (1981) Mécanisme d'elimination rénale de deux éléments du groupe IIIA de la classification périodique: I'aluminium et l'indium. C R Acad Sci Paris 292: 91–96

    Google Scholar 

  18. Galle P, Berry J-P, Duckett S (1980) Electron microprobe ultrastructural localization of aluminum in rat brain. Acta Neuropathol (Berl) 49: 245–247

    Google Scholar 

  19. Galle P, Giudicelli CP, Nebout T, Baglin A, Fries D (1987) Ultrastructural localization of aluminum in hepatocytes of hemodialyzed patients. Ann Pathol 7: 163–170

    Google Scholar 

  20. Gilbert MR, Harding BL, Hoffman PN, Griffin JW, Price DL, Troncoso JC (1992) Aluminum-induced neurofilamentous changes in cultured rat dorsal root ganlia explants. J Neurosci 12: 1763–1771

    Google Scholar 

  21. Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol 31: 286–292

    Google Scholar 

  22. Goodison KL, Parhad IM, White CL, Sima AA, Clark AW (1993) Neuronal and glial gene expression in neocortex of Down's syndrome and Alzheimer's disease. J Neuropathol Exp Neurol 52: 192–198

    Google Scholar 

  23. Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88: 49–92

    Google Scholar 

  24. Hewitt CC, Herman MM, Lopes MBS, Savory J, Wills MR (1991) Aluminium maltol-induced neurocytoskeletal changes in fetal rabbit midbrain in matrix culture. Neuropathol Appl Neurobiol 17: 47–60

    Google Scholar 

  25. Jellinger K, Braak H, Braak E, Fischer P (1991) Alzheimer lesions in the entorhinal region and isocortex in Parkinson's and Alzheimer's diseases. Ann NY Acad Sci 640: 203–209

    Google Scholar 

  26. Johnson GVW, Jope RS (1988) Phosphorylation of rat brain cytoskeletal proteins is increased after orally administered aluminum. Brain Res 456: 95–103

    Google Scholar 

  27. Johnson GVW, Watson AL, Lartius R, Uemura E, Jope RS (1992) Dietary aluminum selectively decreases MAP-2 in brains of developing and adult rats. Neurotoxicology 13: 463–474

    Google Scholar 

  28. Katsetos CD, Savory J, Herman MM, Carpenter RM, Frankfurter A, Hewitt CD, Wills MR (1990) Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits. Neuropathol Appl Neurobiol 16: 511–528

    Google Scholar 

  29. Kisby GE, Acosta D (1987) Cytotoxic effects of aluminum in hippocampal, cerebellar, and astrocyte cell cultures. In Vitro Toxicol 1: 85–102

    Google Scholar 

  30. Klatzo I, Wisniewski H, Streicher E (1965) Experimental production of neurofibrillary degeneration. J Neuropathol Expl Neurol 24: 187–199

    Google Scholar 

  31. Knutti R (1984) Matrixmodifikation zur direkten Bestimmung von Elementen im Ultraspurenbereich in Blut und Urin mittels Graphitrohr-Atomabsorptionsspektrometrie. In: Welz B (ed) Fortschritte in der atomspektrometrischen Spurenanalytik, vol 1. Verlag Chemie, Weinheim, pp 327–336

    Google Scholar 

  32. Kosik KW, Bradley WG, Goof PF, Rasool RG, Selkoe DJ (1983) Cholinergic function in lumbar aluminum myelopathy. J Neuropathol Exp Neurol 42: 365–375

    Google Scholar 

  33. Kosik KS, Duffy LK, Dowling MM, Abraham C, McCluskey A, Selkoe DJ (1984) Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles. Proc Natl Acad Sci USA 81: 7941–7945

    Google Scholar 

  34. Kowall NW, Pendlebury WW, Kessler JB, Perl DP, Beal MF (1989) Alumium-induced neurofibrillary degeneration affects a subset of neurons in rabbit cerebral cortex, basal forebrain and upper brainstem. Neuroscience 29: 329–337

    Google Scholar 

  35. Landsberg JP, McDonald B, Watt F (1992) Absence of aluminium in neuritic plaque cores in Alzheimer's disease. Nature 360: 65–68

    Google Scholar 

  36. Langui D, Anderson BH, Ulrich J (1988) Effects of aluminium chloride on cultured cells from rat brain hemispheres. Brain Res 438: 67–76

    Google Scholar 

  37. Matus A (1988) Microtubule-associated proteins: their potential role in determining neuronal morphology. Annu Rev Neurosci 11: 29–44

    Google Scholar 

  38. Matus A, Bernhardt R, Hugh-Jones T (1981) High molecular weight microtubule-associated proteins are preferentially associated with dendritic microtubules in brain. Proc Natl Acad Sci USA 78: 3010–3014

    Google Scholar 

  39. Munoz-Garcia D, Pendlebury WW, Kessler JB, Perl DP (1986) An immunocytochemical comparison of cytoskeletal proteins in aluminum-induced and Alzheimer-type neurofibrillary tangles. Acta Neuropathol (Berl) 70: 243–248

    Google Scholar 

  40. Nixon RA, Clarke JF, Logvinenko KB, Tan MKH, Hoult M, Grynspan F (1990) Aluminium inhibits calpain-mediated proteolysis and induces human neurofilament proteins to form protease-resistant high molecular weight complexes. J Neurochem 55: 1950–1959

    Google Scholar 

  41. Norenberg MD, Norenberg LOB, Cowman GA, McCarthy M, Neary JT (1989) The effects of aluminum on astrocytes in primary culture. J Neuropathol Exp Neurol 48: 374

    Google Scholar 

  42. O'Callaghan JP, Jensen KF (1992) Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. Neurotoxicology 13: 113–122

    Google Scholar 

  43. Perry G, Rizzuto N, Autilio-Gambetti L, Gambetti P (1985) Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proc Natl Acad Sci USA 82: 3916–3920

    Google Scholar 

  44. Pierce (1990) Immuno Technology, catalog & handbook. Pierce Chemical Company, The Netherlands

    Google Scholar 

  45. Somerville MJ, Percy ME, Bergeron C, Yoong LK, Grima EA, McLachlan DR (1991) Localization and quantitation of 68 kDa neurofilament and superoxide dismutase-1 mRNA in Alzheimer brains. Brain Res [Mol Brain Res] 9: 1–8

    Google Scholar 

  46. Strong MJ, Garruto RM (1991) Neuron-specific thresholds of aluminum toxicity invitro: a comparative analysis of dissociated fetal rabbit hippocampal and motor neuron-enriched cultures. Lab Invest 65: 243–249

    Google Scholar 

  47. Takeda M, Tatebayashi Y, Tanimukai S, Nakamura Y, Tanaka T, Nishimura T (1991) Immunohistochemical study of microtubule-associated protein-2 and ubiquitin in chronically aluminum-intoxicated rabbit brain. Acta Neuropathol 82: 346–352

    Google Scholar 

  48. Troncoso JC, Sternberger NH, Sternberger LA, Hoffman PN, Price DL (1986) Immunocytochemical studies of neurofilament antigens in the neurofibrillary pathology induced by aluminum. Brain Res 364: 295–300

    Google Scholar 

  49. Walz W (1989) Role of glial cells in the regulation of the brain ion microenvironment. Prog Neurobiol 33: 309–333

    Google Scholar 

  50. Wisniewski HM (1991) Neuropathology and biochemistry of Alzheimer's disease and aluminium encephalopathy. In: Detchant Lord Walton (ed) Alzheimer's disease and the environment. Royal Society of Medicine Services,London, pp 35–38

    Google Scholar 

  51. Zubenko GS,Hanin I (1989) Cholinergic and noradrenergic toxicity of intraventricular aluminum chloride in the rat hipocampus. Brain Res 498: 381–384

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Toxicology, ETH and University of Zürich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland

    Judith Pia Müller & Arend Bruinink

Authors
  1. Judith Pia Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arend Bruinink
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study is part of the Ph. D. thesis of Judith P. Mueller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, J.P., Bruinink, A. Neurotoxic effects of aluminium on embryonic chick brain cultures. Acta Neuropathol 88, 359–366 (1994). https://doi.org/10.1007/BF00310380

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00310380

Key words

Search

Navigation