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Neurochemical Research

, Volume 33, Issue 11, pp 2294–2301 | Cite as

Effect of Long-Term Exposure to Aluminum on the Acetylcholinesterase Activity in the Central Nervous System and Erythrocytes

  • R. R. Kaizer
  • M. C. Corrêa
  • L. R. S. Gris
  • C. S. da Rosa
  • D. Bohrer
  • V. M. Morsch
  • Maria Rosa Chitolina Schetinger
Original Paper

Abstract

Aluminum (Al), a neurotoxic agent, has been associated with Alzheimer’s disease (AD), which is characterized by cholinergic dysfunction in the central nervous system. In this study, we evaluated the effect of long-term exposure to aluminum on acetylcholinesterase (AChE) activity in the central nervous system in different brain regions, in synaptosomes of the cerebral cortex and in erythrocytes. The animals were loaded by gavage with AlCl3 50 mg/kg/day, 5 days per week, totalizing 60 administrations. Rats were divided into four groups: (1) control (C); (2) 50 mg/kg of citrate solution (Ci); (3) 50 mg/kg of Al plus citrate (Al + Ci), and (4) 50 mg/kg of Al (Al). AChE activity in striatum was increased by 15% for Ci, 19% for Al + Ci and 30% for Al, when compared to control (P < 0.05). The activity in hypothalamus increased 23% for Ci, 26% for Al + Ci and 28% for Al, when compared to control (P < 0.05). AChE activity in cerebellum, hippocampus and cerebral cortex was decreased by 11%, 23% and 21% respectively, for Al, when compared to the respective controls (P < 0.05). AChE activity in synaptosomes was increased by 14% for Al, when compared to control (P < 0.05). Erythrocyte AChE activity was increased by 17% for Al + Ci and 11% for Al, when compared to control (P < 0.05). These results indicate that Al affects at the same way AChE activity in the central nervous system and erythrocyte. AChE activity in erythrocytes may be considered a marker of easy access of the central cholinergic status.

Keywords

Aluminum Acetylcholinesterase (AChE) Alzheimer’s Disease (AD) Synaptosomes Erythrocyte 

Notes

Acknowledgments

This study was supported by CNPq, FAPERGS, CAPES, Federal University of Santa Maria, and FINEP research grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)”.

References

  1. 1.
    Hopkin SP (1989) Ecophysiology of metals in terrestrial invertebrates. Elsevier, New YorkGoogle Scholar
  2. 2.
    Kaizer RR, Maldonado PA, Spanevello RM et al (2007) The effect of aluminium on NTPDase and 5′-nucleotidase activities from rat synaptosomes and platelets. Int J Dev Neurosci 25:381–386PubMedCrossRefGoogle Scholar
  3. 3.
    Saiyed SM, Yokel RA (2005) Aluminium content of some foods and food products in the USA, with aluminium food additives. Food Additiv Contam 22:234–244CrossRefGoogle Scholar
  4. 4.
    Yokel RA (2000) The toxicology of aluminum in the brain: a review. Neurotoxicology 21:813–828PubMedGoogle Scholar
  5. 5.
    Exley C (2001) Why is research into aluminum and life important? In: Exley C (ed) Aluminum and Alzheimer’s disease. Elsevier, Amsterdam, pp v–viiiCrossRefGoogle Scholar
  6. 6.
    Xu N, Majidi V, Markesbery WR (1992) Brain aluminium in Alzheimer’s disease using an improved GFAAS method. Neurotoxicology 13:735–743PubMedGoogle Scholar
  7. 7.
    Candy JM, Klinowski J, Perry RH et al (1986) Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1:354–357PubMedCrossRefGoogle Scholar
  8. 8.
    Geula C, Mesulam MM (1999) Cholinergic systems in Alzheimer’s disease. In: Terry RD, Katzman R, Bick KL, Sisodia SS (eds) Alzheimer Disease. Lippincott Williams & Wilkins, Philadelphia, pp 269–292Google Scholar
  9. 9.
    Zatta P, Ibn-Lkhayat-Idrissi M, Zambenedetti P et al (2002) In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase. Brain Res Bull 59:41–45PubMedCrossRefGoogle Scholar
  10. 10.
    Kaizer RR, Corrêa MC, Spanevello RM et al (2005) Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 99:1865–1870PubMedCrossRefGoogle Scholar
  11. 11.
    Grisaru D, Sternfeld M, Eldor A et al (1999) Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem 264:672–686PubMedCrossRefGoogle Scholar
  12. 12.
    Ahmed M, Rocha JBT, Corrêa M et al (2006) Inhibition of two different cholinesterases by tacrine. Chem Biol Interact 162:165–171PubMedCrossRefGoogle Scholar
  13. 13.
    Kaizer RR, Silva AC, Morsch VM et al (2004) Diet-induced changes in AChE activity after long-term exposure. Neurochem Res 29:2251–2255PubMedCrossRefGoogle Scholar
  14. 14.
    Gulya K, Rakonczay Z, Kasa P (1990) Cholinotoxic effects of aluminium in rat brain. J Neurochem 54:1020–1026PubMedCrossRefGoogle Scholar
  15. 15.
    Nayak P (2002) Aluminum: impacts and disease. Environ Res 89:101–115PubMedCrossRefGoogle Scholar
  16. 16.
    Mesulam MM, Moran MA (1987) Cholinesterases within neurofibrillary tangles related to age and Alzheimer’s disease. Ann Neurol 22:223–228PubMedCrossRefGoogle Scholar
  17. 17.
    Rakonczay Z, Horváth Z, Juhász A et al (2005) Peripheral cholinergic disturbances in Alzheimer’s disease. Chem Biol Interact 157–158:233–238PubMedCrossRefGoogle Scholar
  18. 18.
    Mazzanti CM, Spanevello RM, Pereira LB et al (2006) Acetylcholinesterase activity in rats experimentally demyelinated with ethidium bromide and treated with interferon beta. Neurochem Res 31:1027–1034PubMedCrossRefGoogle Scholar
  19. 19.
    Mazzanti CM, Spanevello RM, Obregon A et al (2006) Ethidium bromide inhibits rat brain acetylcholinesterase activity in vitro. Chem Biol Interact 25:121–127CrossRefGoogle Scholar
  20. 20.
    Milatovic D, Dettbarn WD (1996) Modification of acetylcholinesterase during adaptation to chronic, subacute paraoxon application in rat. Toxicol Appl Pharmacol 136:20–28PubMedCrossRefGoogle Scholar
  21. 21.
    Missel JR, Schetinger MR, Gioda CR et al (2005) Chelating effect of novel pyrimidines in a model of aluminium intoxication. J Inorg Biochem 99:1853–1857PubMedCrossRefGoogle Scholar
  22. 22.
    Schetinger MRC, Bonan CD, Morsch VM et al (1999) Effects of aluminium sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice. Braz J Med Biol Res 32:761–766PubMedCrossRefGoogle Scholar
  23. 23.
    Exley C (2004) The pro-oxidant activity of aluminium. Free Radic Biol Med 36:380–387PubMedCrossRefGoogle Scholar
  24. 24.
    Bohrer D, Dessuy MB, Kaizer R, Nascimento PC, Schetinger MRC, Morsch VM, Carvalho LM, Garcia SC (2008) Tissue digestion for aluminum determination in experimental animal studies. Anal. Biochem. In press.Google Scholar
  25. 25.
    Nagy A, Delgado-Escueta AV (1984) Rapid preparation of synaptosomes from mammalian brain using nontoxic isosmotic gradient material (Percoll). J Neurochem 43:1114–1123PubMedCrossRefGoogle Scholar
  26. 26.
    Ellman GL, Courtney DK, Andres V et al (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95PubMedCrossRefGoogle Scholar
  27. 27.
    Rocha JBT, Emmanuelli T, Pereira ME (1993) Effects of early undernutrition on kinetic parameters of brain acetylcholinesterase from adult rats. Acta Neurobiol Exp 53:431–437Google Scholar
  28. 28.
    Worek F, Mast U, Kiderlen D et al (1999) Improved determination of acetylcholinesterase activity in human whole blood. Clin Chim Acta 288:73–90PubMedCrossRefGoogle Scholar
  29. 29.
    Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:218–254CrossRefGoogle Scholar
  30. 30.
    Yates CM, Simpson J, Russell D et al (1980) Cholinergic enzymes in neurofibrillary degeneration produced by aluminium. Brain Res 197:269–274PubMedCrossRefGoogle Scholar
  31. 31.
    Beauchemin D, Kisilevsky R (1998) A method based on ICP-MS for the analysis of Alzheimer’s amyloid plaques. Anal Chem 70:1026–1029PubMedCrossRefGoogle Scholar
  32. 32.
    Roberts NB, Clough A, Bellia JP et al (1998) Increased absorption of aluminium from a normal dietary intake in dementia. J Inorg Biochem 69:171–176PubMedCrossRefGoogle Scholar
  33. 33.
    Schönholzer KW, Sutton RAL, Walker VR et al (1997) Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry. Clin Sci 92:379–383PubMedGoogle Scholar
  34. 34.
    Powell JJ, Thompson RPH (1993) The chemistry of aluminium in the gastrointestinal lumen and its uptake and absorption. Proc Nutr Soc 52:241–253PubMedCrossRefGoogle Scholar
  35. 35.
    Greger JL, Chang MM, MacNeil GG (1994) Tissue turnover of aluminum and Ga–67, effect of iron status. Proc Soc Exper Biol Med 207:89–96Google Scholar
  36. 36.
    Banks WA, Kastin AJ (1989) Aluminum-induced neurotoxicity: alterations in membrane function at the blood-brain barrier. Neurosci Biobehav Rev 13:47–53PubMedCrossRefGoogle Scholar
  37. 37.
    van Rensburg SJ, Potocnick CV, Taljaard JJF (1995) In: Zatta P, Nicolini M (eds) Nonneuronal cells in AD, World Scientific, Singapore, pp 25–30Google Scholar
  38. 38.
    Silva VS, Cordeiro M, Matos MJ et al (2002) Aluminum accumulation and membrane fluidity alteration in synaptosomes isolated from rat brain cortex following aluminum ingestion: effect of cholesterol. Neurosci Res 44:181–193PubMedCrossRefGoogle Scholar
  39. 39.
    Swegert CV, Dave KR, Katyare SS (1999) Effect of aluminium-induced Alzheimer like condition on oxidative energy metabolism in rat liver, brain and heart mitochondria. Mech Ageing Dev 112:27–42PubMedCrossRefGoogle Scholar
  40. 40.
    Massoulié J, Pezzementi L, Bon S et al (1993) The molecular and cellular biology of cholinesterase. Prog Neurobiol 41:31–91PubMedCrossRefGoogle Scholar
  41. 41.
    Atack JR, Perry EK, Bonhan JR et al (1983) Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form. Neurosci Lett 40:199–204PubMedCrossRefGoogle Scholar
  42. 42.
    Julka D, Gill KD (1996) Altered calcium homeostasis: a possible mechanism of aluminium-induced neurotoxicity. Biochim Biophys Acta 1315:47–54PubMedGoogle Scholar
  43. 43.
    Nicholls DM, Speares GM, Miller ACM et al (1991) Brain protein synthesis in rabbits following low level aluminium exposure. Int J Biochem 23:737–741PubMedCrossRefGoogle Scholar
  44. 44.
    Kumar S (1998) Biphasic effect of aluminium on cholinergic enzyme of rat brain. Neurosc Lett 248:121–123CrossRefGoogle Scholar
  45. 45.
    von Benhardi R, Ramírez G, De Ferrari GV et al (2003) Acetylcholinesterase induces the expression of the β-amyloid precursors protein in glia and activates glial cells in culture. Neurobiol Dis 14:447–457CrossRefGoogle Scholar
  46. 46.
    Campbell A, Kumar A, La Rosa FG et al (2000) Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells. Proc Soc Exp Biol Med 223:397–402PubMedCrossRefGoogle Scholar
  47. 47.
    Exley C, Korchazhkina OV (2001) Promotion of formation of amyloid fibrils by aluminium adenosine triphosphate (AlATP). J Inorg Biochem 84:215–224PubMedCrossRefGoogle Scholar
  48. 48.
    Silva VS, Gonçalves PP (2003) The inhibitory effect of aluminium on the (Na+/K+) ATPase activity of rat brain cortex synaptosomes. J Inorg Biochem 97:143–150PubMedCrossRefGoogle Scholar
  49. 49.
    Wright CI, Geula C, Mesulam MM (1993) Neurological cholinesterases in the normal brain and in Alzheimer’s disease: relationship to plaques, tangles, and patterns of selective vulnerability. Ann Neurol 34:373–384PubMedCrossRefGoogle Scholar
  50. 50.
    Simpson J, Yates CM, Whyler DK et al (1985) Biochemical studies on rabbits with aluminium induced neurofilament accumulation. Neurochem Res 10:229–238PubMedCrossRefGoogle Scholar
  51. 51.
    De Ferrari GV, Canales MA, Shin I et al (2001) A structural motif of acetylcholinesterase that promotes amyloid-β-peptide fibril formation. Biochemistry 40:10447–10457PubMedCrossRefGoogle Scholar
  52. 52.
    Bartoli M, Bertucci C, Cavrini V et al (2003) Beta-amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem Pharmacol 65:407–416CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • R. R. Kaizer
    • 1
  • M. C. Corrêa
    • 1
  • L. R. S. Gris
    • 2
  • C. S. da Rosa
    • 1
  • D. Bohrer
    • 2
  • V. M. Morsch
    • 1
  • Maria Rosa Chitolina Schetinger
    • 1
    • 2
  1. 1.Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa Maria, Campus UniversitárioSanta MariaBrazil
  2. 2.Departamento de Química, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa Maria, Campus UniversitárioSanta MariaBrazil

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