Skip to main content

Advertisement

Log in

Aluminium neurotoxicity: neurobehavioural and oxidative aspects

  • Review Article
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Aluminium is the most widely distributed metal in the environment and is extensively used in daily life that provides easy exposure to human beings. The exposure to this toxic metal occurs through air, food and water. However, there is no known physiological role for aluminium within the body and hence this metal may produce adverse physiological effects. Chronic exposure of animals to aluminium is associated with behavioural, neuropathological and neurochemical changes. Among them, deficits of learning and behavioural functions are most evident. Some epidemiological studies have shown poor performance in cognitive tests and a higher abundance of neurological symptoms for workers occupationally exposed to aluminium. However, in contrast to well established neurotoxic effects, neurobehavioural studies of aluminium in rodents have generally not produced consistent results. Current researches show that any impairment in mitochondrial functions may play a major role in many human disorders including neurodegenerative disorders. Being involved in the production of reactive oxygen species, aluminium may cause impairments in mitochondrial bioenergetics and may lead to the generation of oxidative stress which may lead to a gradual accumulation of oxidatively modified cellular proteins. In this review, the neuropathologies associated with aluminium exposure in terms of neurobehavioural changes have been discussed. In addition, the impact of aluminium on the mitochondrial functions has also been highlighted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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

  • Abramov AY, Canevari C, Duchen MR (2004) Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci 24:565–575

    Article  PubMed  CAS  Google Scholar 

  • Ackley DC, Yokel RA (1998) Aluminium transport out of brain extracellular fluid is proton dependent and inhibited by mersalyl acid, suggesting mediation by the monocarboxylate transporter (MCT1). Toxicology 127:59–67

    Article  PubMed  CAS  Google Scholar 

  • Akila R, Stollery BT, Riihimäki V (1999) Decrements in cognitive performance in metal inert gas welders exposed to aluminium. Occup Environ Med 56:632–639

    Article  PubMed  CAS  Google Scholar 

  • Alfrey AC (1978) Dialysis encephalopathy syndrome. Annu Rev Med 29:93–98

    Article  PubMed  CAS  Google Scholar 

  • Alfrey AC (1980) Aluminium metabolism in uremia. Neurotoxicology 1:43–53

    CAS  Google Scholar 

  • Alfrey A (1983) Aluminium. Adv Clin Chem 23:59–91

    Google Scholar 

  • Alfrey AC, Hegg A, Craswell P (1980) Metabolism and toxicity of aluminium in renal failure. Am J Clin Nutr 33:1509–1516

    PubMed  CAS  Google Scholar 

  • Alleva E, Rankin J, Santucci D (1998) Neurobehavioral alteration in rodents following developmental exposure to aluminium. Toxicol Ind Health 14:209–221

    PubMed  CAS  Google Scholar 

  • Anthony J, Fadl S, Mason C, Davidson A, Berry J (1986) Absorption, deposition and distribution of dietary aluminium in immature rats: Effects of dietary vitamin D3 and food-borne chelating agent. J Environ Sci Health B21:191–205

    CAS  Google Scholar 

  • Antonini JM, O’callaghan JP, Miller DB (2006) Development of an animal model to study the potential neurotoxic effects associated with welding fume inhalation. Neurotoxicology 27:745–751

    Article  PubMed  CAS  Google Scholar 

  • Arieff AI, Copper JD, Armstrong D, Lazarowitz VC (1979) Dementia, renal failure and brain aluminium. Ann Inter Med 90:741–747

    CAS  Google Scholar 

  • Atienzar F, Desor D, Burnel D, Keller JM, Lehr P, Vasseur F (1998) Effect of aluminium on superoxide dismutase activity in the adult rat brain. Biol Trace Elem Res 65:19–30

    Article  PubMed  CAS  Google Scholar 

  • Bakir AA, Hryhorczuk DO, Berman E, Dunea G (1986) Acute fatal hyperaluminemic encephalopathy in undialyzed and recently dialyzed uremic patients. ASAIO Trans 32:171–176

    PubMed  CAS  Google Scholar 

  • Banks WA, Niehoff ML, Drago D, Zatta P (2006) Aluminium complexing enhances amyloid beta protein penetration of blood-brain barrier. Brain Res 1116:215–221

    Article  PubMed  CAS  Google Scholar 

  • Bartus RT, Dean RL 3rd, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–414

    Article  PubMed  CAS  Google Scholar 

  • Baydar T, Papp A, Aydin A, Nagymajtenyi L, Schulz H, Isimer A, Sahin G (2003) Accumulation of aluminium in rat brain: does it lead to behavioral and electrophysiological changes? Biol Trace Elem Res 92:231–244

    Article  PubMed  CAS  Google Scholar 

  • Becaria A, Campbell A, Bondy SC (2002) Aluminium as a toxicant. Toxicol Ind Health 18:309–320

    Article  PubMed  CAS  Google Scholar 

  • Beckman KB, Ames BN (1998) Mitochondrial aging: open questions. Ann NY Acad Sci 854:118–127

    Article  PubMed  CAS  Google Scholar 

  • Berlyne GM, Yagil R, Ben-Ari J, Weinberger G, Knoff E, Danovitch GM (1972) Aluminium toxicity to rats. Lancet 1:564–568

    Article  PubMed  CAS  Google Scholar 

  • Bertholf R, Herman M, Savory J, Carpenter R, Sturgill CB, Katsetos CD, Vandenberg SR, Wills M (1989) A long-term intravenous model of aluminium maltol toxicity in rabbits: tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure. Toxicol Appl Pharmacol 98:58–74

    Article  PubMed  CAS  Google Scholar 

  • Berthon G (1996) Chemical speciation studies in relation to aluminium metabolism and toxicity. Coord Chem Rev 149:241–280

    CAS  Google Scholar 

  • Bharath S, Andersen JK (2005) Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line results in limited tyrosine nitration of mitochondrial complex I subunits: implications for Parkinson’s disease. Antioxid Redox Signal 7:900–910

    Article  PubMed  CAS  Google Scholar 

  • Bolla KI, Briefel G, Spector D, Schwartz BS, Wieler L, Herron J, Gimenez L (1992) Neurocognitive effects of aluminium. Arch Neurol 49:1021–1026

    PubMed  CAS  Google Scholar 

  • Bondy SC, Kirstein S (1996) The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminium. Mol Chem Neuropathol 27:185–194

    Article  PubMed  CAS  Google Scholar 

  • Bondy SC, Guo-Ross SX, Pien J (1998) Mechanisms underlying the aluminium-induced potentiation of the prooxidant properties of transition metals. Neurotoxicology 19:65–71

    PubMed  CAS  Google Scholar 

  • Bosetti F, Solaini G, Tendi EA, Chikhale EG, Chandrasekaran K, Rapoport SI (2001) Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminium exposure in PC12S cells. Neuroreport 12:721–724

    Article  PubMed  CAS  Google Scholar 

  • Bowdler NC, Beasley DS, Fritze EC, Goulette AM, Hatton JD, Hession J, Ostman DL, Rugg DJ, Schmittdiel CJ (1979) Behavioral effects of aluminium ingestion on animal and human subjects. Pharmacol Biochem Behav 10:505–512

    Article  PubMed  CAS  Google Scholar 

  • Buchta M, Kiesswetter E, Otto A, Schaller KH, Seeber A, Hilla W, Windorfer K, Stork J, Kuhlmann A, Geeller O, Letzel S (2003) Longitudinal study examining the neurotoxicity of occupational exposure to aluminium containing welding fumes. Int Arch Occup Environ Health 76:539–548

    Article  PubMed  CAS  Google Scholar 

  • Buchta M, Kiesswetter E, Scha¨per M, Zschiesche W, Schaller KH, Kuhlmanna A, Letzel S (2005) Neurotoxicity of exposures to aluminium welding fumes in the truck trailer construction industry. Environ Toxicol Pharmacol 19:677–685

    Article  CAS  Google Scholar 

  • Bushinsky DA, Sprague SM, Hallegot P, Girod C, Chabala JM, Levi-Setti R (1995) Effects of aluminium on bone surface ion composition. J Bone Miner Res 10:1988–1997

    Article  PubMed  CAS  Google Scholar 

  • Calabrese V, Lodi R, Tonon C, D’Agata V, Sapienza M, Scapagnini G, Mangiameli A, Pennisi G, Stella AM, Butterfield DA (2005) Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J Neurol Sci 233:145–162

    Article  PubMed  CAS  Google Scholar 

  • Campbell A, Prasad KN, Bondy SC (1999) Aluminium-induced oxidative events in cell lines: glioma are more responsive than neuroblastoma. Free Rad Biol Med 26:1166–1171

    Article  PubMed  CAS  Google Scholar 

  • Campbell A, Hamai D, Bondy SC (2001) Differential toxicity of aluminium salts in human cell lines of neural origin: implications for neurodegeneration. Neurotoxicology 22:63–71

    Article  PubMed  CAS  Google Scholar 

  • Candan N, Tuzmen N (2008) Very rapid quantification of malondialdehyde (MDA) in rat brain exposed to lead, aluminium and phenolic antioxidants by high-performance liquid chromatography-fluorescence detection. Neurotoxicology 29:708–713

    Article  PubMed  CAS  Google Scholar 

  • Candura SM, Manzo L, Costa LG (1998) Role of occupational neurotoxicants in psychiatric and neurodegenerative disorders. In: Costa LG, Manzo L (eds) Occupational neurotoxicology. CRC Press, Boca Raton, pp 131–167

    Google Scholar 

  • Chan JCM, Jacob M, Brown S, Savory J, Wills MR (1988) Aluminium metabolism in rats; effects of vitamin D dihydrocortisol, 1, 25-dihydroxyvitamin D and phosphate binders. Nephron 48:61–64

    Article  PubMed  CAS  Google Scholar 

  • Circu ML, Aw TY (2008) Glutathione and apoptosis. Free Radic Res 42:689–706

    Article  PubMed  CAS  Google Scholar 

  • Clarkson EM, Luck VA, Hynson WV, Bailey RR, Eastwood JB, Clements JS (1972) The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances, the serum parathyroid concentrations and the aluminium content of bone in patients with chronic renal failure. Clin Sci 43:519–531

    PubMed  CAS  Google Scholar 

  • Clauberg M, Joshi JG (1992) Effects of prolonged chronic dietary treatment with AlCl3 on selected metabolisms and memory in rats. Ann N Y Acad Sci 648:289–290

    Article  PubMed  CAS  Google Scholar 

  • Cochran M, Eliott DC, Brennan P, Chawtur V (1990) Inhibition of protein kinase C activation by low concentrations of aluminium. Clin Chim Acta 194:167–172

    Article  PubMed  CAS  Google Scholar 

  • Colomina MT, Roig JL, Sanchez DL, Domingo JL (2002) Influence of age on aluminium induced neurobehavioural effects of changes in rat brain. Neurotoxicology 23:775–781

    Article  PubMed  CAS  Google Scholar 

  • Colomina MT, Roig JL, Torrente M, Vicens P, Domingo JL (2005) Concurrent exposure to aluminium and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring. Neurotoxicol Teratol 27:565–574

    Article  PubMed  CAS  Google Scholar 

  • Connor DJ, Jope RS, Harrell LE (1988) Chronic, oral aluminium administration to rats: cognition and cholinergic parameters. Pharmacol Biochem Behav 31:467–474

    Article  PubMed  CAS  Google Scholar 

  • Connor DJ, Harrell LE, Jope RS (1989) Reversal of an aluminium-induced behavioral deficit by administration of deferoxamine. Behav Neurosci 103:779–783

    Article  PubMed  CAS  Google Scholar 

  • Corain B, Bombi GG, Tapparo A, Perazzolo M, Zatta P (1996) Aluminium toxicity and metal speciation: established data and open questions. Coord Chem Rev 149:11–22

    CAS  Google Scholar 

  • Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminium distribution in Alzheimer’s disease and experimental neurofibrillary degeneration. Science 180:511–513

    Article  PubMed  CAS  Google Scholar 

  • Dave KR, Syal AR, Katyare SS (2002) Effect of long-term aluminium feeding on kinetics attributes of tissue cholinesterases. Brain Res Bull 58:225–233

    Article  PubMed  CAS  Google Scholar 

  • De Marchi U, Mancon M, Battaglia V, Ceccon S, Cardellini P, Toninello A (2004) Influence of reactive oxygen species production by monoamine oxidase activity on aluminium-induced mitochondrial permeability transition. Cell Mol Life Sci 61:2664–2671

    Article  PubMed  CAS  Google Scholar 

  • Dewitt DA, Hurd JA, Fox N, Townsend BE, Griffioen KJ, Ghribi O, Savory J (2006) Peri-nuclear clustering of mitochondria is triggered during aluminium maltolate induced apoptosis. J Alzheimer Dis 9:195–205

    Google Scholar 

  • Domingo JL (1995) Reproductive and developmental toxicity of aluminium: a review. Neurotoxicol Teratol 17:515–521

    Article  PubMed  CAS  Google Scholar 

  • Domingo JL, Llorens J, Sanchez DJ, Gomez M, Llobet JM, Corbella J (1996) Age-related effects of aluminium ingestion on brain aluminium accumulation and behavior in rats. Life Sci 58:1387–1395

    Article  PubMed  CAS  Google Scholar 

  • Duan J, Karmazyn M (1992) Protective effects of amiloride on the ischemic reperfused rat heart. Relation to mitochondrial function. Eur J Pharmacol 210:149–157

    Article  PubMed  CAS  Google Scholar 

  • Exley C (2004) The pro-oxidant activity of aluminium. Free Radic Biol Med 36:380–387

    Article  PubMed  CAS  Google Scholar 

  • Flendrig JA, Kruis H, Das HA (1976) Aluminium and dialysis dementia. Lancet 1:1235

    Article  PubMed  CAS  Google Scholar 

  • Fulton B, Jaw S, Jeffery EH (1989) Bioavailability of aluminium from drinking water. Fundam Appl Toxicol 12:144–150

    Article  PubMed  CAS  Google Scholar 

  • Garruto RM, Fukatsu R, Yanagihara R, Gajdusek DC, Hook G, Fiori CE (1984) Imaging of calcium and aluminium in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci USA 81:1875–1879

    Article  PubMed  CAS  Google Scholar 

  • Giasson BI, Ischiropoulos H, Lee VM, Trojanowski JQ (2002) The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer’s and Parkinson’s diseases. Free Radic Biol Med 32:1264–1275

    Article  PubMed  CAS  Google Scholar 

  • Giorgianni C, Faranda M, Brecciaroli R, Beninato G, Saffioti G, Muraca G et al (2003) Cognitive disorders among welders exposed to aluminium. G Ital Med Lav Ergon 25:102–103

    PubMed  Google Scholar 

  • Gleb MH, Harris DC (1980) Correlation of protein release and ultraviolet difference spectra associated with metal binding with transferring. Arch Biochem Biophys 200:93–98

    Article  Google Scholar 

  • Golub MS, Domingo JL (1996) What we know and what we need to know about developmental aluminium toxicity. J Toxicol Environ Health 48:585–597

    Article  PubMed  CAS  Google Scholar 

  • Golub MS, Germann SL (2001) Long-term consequences of developmental exposure to aluminium in a suboptimal diet for growth and behavior of Swiss Webster mice. Neurotoxicol Teratol 23:365–372

    Article  PubMed  CAS  Google Scholar 

  • Golub MS, Han B, Keen CL, Gershwin ME (1992) Effects of dietary aluminium excess and manganese deficiency on neurobehavioral endpoints in adult mice. Toxicol Appl Pharmacol 112:154–160

    Article  PubMed  CAS  Google Scholar 

  • Golub MS, Germann SL, Han B, Keen CL (2000) Life long feeding of a high aluminium diet to mice. Toxicology 150:107–117

    Article  PubMed  CAS  Google Scholar 

  • Gómez M, Sánchez DJ, Llobet JM, Corbella J, Domingo JL (1997) The effect of age on aluminium retention in rats. Toxicology 116:1–8

    Article  PubMed  Google Scholar 

  • Gonda Z, Lehotzky K (1996) Effect of prenatal aluminium lactate exposure on conditioned taste aversion and passive avoidance task in the rat. J Appl Toxicol 16:529–532

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez MA, Roma M, Bernal C, Alvarez ML, Carrillo MC (2004) Biliary secretory function in rats chronically intoxicated with aluminium. Toxicol Sci 79:189–195

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez MA, Alvarez Mdel L, Pisani GB, Bernal CA, Roma MG, Carrillo MC (2007) Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminium to rats. Biol Trace Elem Res 116:329–348

    Article  PubMed  CAS  Google Scholar 

  • Hantson P et al (1995) Fatal encephalopathy after otoneurosurgery procedure with an aluminum-containing biomaterial. J Toxicol Clin Toxicol 33:645–648

    Article  PubMed  CAS  Google Scholar 

  • Hardy L, Clark JB, Darley-Usmar VM, Smith DR, Stone D (1991) Reoxygenation-dependent decrease in mitochondrial NADH:CoQ reductase (Complex I) activity in the hypoxic/reoxygenated rat heart. Biochem J 274:133–137

    PubMed  CAS  Google Scholar 

  • Holmgren A (1979) Glutathione dependent synthesis of deoxyribonucleotide. Purification and characterization of glutaredoxin from E. Coli. J Biol Chem 254:3664–3671

    PubMed  CAS  Google Scholar 

  • Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225:1168–1170

    Article  PubMed  CAS  Google Scholar 

  • Iregren A, Sjogren B, Gustafsson K, Hagman M, Nylen L, Frech W, Andersson M, Ljunggren KG, Wennberg A (2001) Effects on the nervous system in different groups of workers exposed to aluminium. Occup Environ Med 58:453–460

    Article  PubMed  CAS  Google Scholar 

  • Jack R, Rabin PL, McKinney TD (1984) Dialysis encephalopathy. A Rev Int J Psychiatr Med 13:309–326

    Article  CAS  Google Scholar 

  • Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl.3):S26–S36 (discussion S36–S38)

    Article  PubMed  CAS  Google Scholar 

  • Jing Y, Wang Z, Song Y (2004) Quantitative study of aluminium-induced changes in synaptic ultrastructure in rats. Synapse 52:292–298

    Article  PubMed  CAS  Google Scholar 

  • Johnson VJ, Kim SH, Sharma RP (2005) Aluminium–maltolate induces apoptosis and necrosis in neuro-2a cells: potential role for p53 signaling. Toxicol Sci 83:329–339

    Article  PubMed  CAS  Google Scholar 

  • Julka D, Gill KD (1996) Distribution of aluminium in different regions and body organs of rat. Biol Trace Elem Res 52:181–192

    Article  PubMed  CAS  Google Scholar 

  • Julka D, Sandhir R, Gill KD (1995) Altered cholinergic metabolism in rat CNS following Al exposure: implications on learning performance. J Neurochem 65:2157–2164

    Article  PubMed  CAS  Google Scholar 

  • Jyoti A, Sethi P, Sharma D (2007) Bacopa monniera prevents from aluminium neurotoxicity in the cerebral cortex of rat brain. J Ethnopharmacol 111:56–62

    Article  PubMed  Google Scholar 

  • Kaizer RR, Corrêa MC, Spanevello RM, Morsch VM, Mazzanti CM, Gonçalves JF, Schetinger MR (2005) Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminium on different mouse brain regions. J Inorg Biochem 99:1865–1870

    Article  PubMed  CAS  Google Scholar 

  • Kaizer RR, Corrêa MC, Gris LR, da Rosa CS, Bohrer D, Morsch VM, Schetinger MR (2008) Effect of long-term exposure to aluminium on the acetylcholinesterase activity in the central nervous system and erythrocytes. Neurochem Res 33:2294–2301

    Article  PubMed  CAS  Google Scholar 

  • Kaneko N, Yasui H, Takada J, Suzuki K, Sakurai K (2004) Orally administrated aluminium–maltolate complex enhances oxidative stress in the organs of mice. J Inorg Biochem 98:2022–2031

    Article  PubMed  CAS  Google Scholar 

  • Kaneko N, Sugioka T, Sakurai H (2007) Aluminium compounds enhance lipid peroxidation in liposomes: insight into cellular damage caused by oxidative stress. J Inorg Biochem 101:967–975

    Article  PubMed  CAS  Google Scholar 

  • Kaur A, Joshi K, Walker RM, Gill KD (2006) Neurofilament phosphorylation and disruption: a possible mechanism of chronic aluminium toxicity in Wistar rats. Toxicology 219:1–10

    Article  PubMed  CAS  Google Scholar 

  • Kawahara M (2005) Effect of aluminium on the nervous system and its possible link with neurodegenerative diseases. J Alzheimer Dis 8:171–182

    CAS  Google Scholar 

  • Keller JN, Kindy MS, Holtsberg FW, St Clair DK, Yen HC, Germeyer A et al (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci 18:687–697

    PubMed  CAS  Google Scholar 

  • Kiesswetter E, Schäper M, Buchta M, Schaller KH, Rossbach B, Scherhag H, Zschiesche W, Letzel S (2007) Longitudinal study on potential neurotoxic effects of aluminium: I. Assessment of exposure and neurobehavioural performance of Al welders in the train and truck construction industry over 4 years. Int Arch Occup Environ Health 81:41–67

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Bal A, Gill KD (2008) Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium. Brain Res 1232:94–103

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Bal A, Gill KD (2009) Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage. Toxicology 255:117–123

    Article  PubMed  CAS  Google Scholar 

  • Lal B, Gupta A, Murthy RC, Ali MM, Chandra SV (1993) Aluminium ingestion alters behavior and some neurochemicals in rats. Ind J Exp Biol 31:30–35

    CAS  Google Scholar 

  • Leuner K, Hauptmann S, Abdel-Kader R, Scherping I, Keil U, Strosznajder JB, Eckert A, Muller WE (2007) Mitochondrial dysfunction: the first domino in brain aging and Alzheimer’s disease? Antioxid Redox Signal 9:1659–1675

    Article  PubMed  CAS  Google Scholar 

  • Li XP, Yang YJ, Hu H, Wang QN (2006) Effect of aluminium trichloride on dissociated Ca2+ in Hippocampus neuron cell as well as learning and memory. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 24:161–163

    PubMed  CAS  Google Scholar 

  • Lione A (1985) Aluminium toxicity and the aluminium containing medication. Pharmacol Ther 29:255–285

    Article  PubMed  CAS  Google Scholar 

  • Maeda M, Takagi H, Hattori H, Matsuzaki T (1997) Localization of manganese superoxide dismutase in the cerebral cortex and hippocampus of Alzheimer-type senile dementia. Osaka City Med J 43:1–5

    PubMed  CAS  Google Scholar 

  • Mahieu S, Gionotti M, Millen N, Elias MM (2003) Effect of chronic accumulation of aluminium on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats. Arch Toxicol 77:605–612

    Article  PubMed  CAS  Google Scholar 

  • Mailloux RJ, Hamel R, Appanna VD (2006) Aluminium toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes. J Biochem Mol Toxicol 20:198–208

    Article  PubMed  CAS  Google Scholar 

  • Mailloux R, Lemire J, Appanna V (2007) Aluminium-induced mitochondrial dysfunction leads to lipid accumulation in human hepatocytes: a link to obesity. Cell Physiol Biochem 20:627–638

    Article  PubMed  CAS  Google Scholar 

  • Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic boil Med 23:134–147

    Article  CAS  Google Scholar 

  • Marklund SL (1982) Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci USA 79:7634–7638

    Article  PubMed  CAS  Google Scholar 

  • Marsden SNE, Parkinson IS, Ward MK, Ellis HA, Kerr DNS (1979) Evidence for aluminium accumulation in renal failure. Proc Eur Dial Transplant Assoc 16:588–596

    PubMed  CAS  Google Scholar 

  • McDermoth JR, Smith AI, Iqbal K, Wisniewski HM (1979) Brain aluminium in aging and Alzheimer’s disease. Neurology 29:809–814

    Google Scholar 

  • McLachlan DR, Bergeron C, Smith JE, Boomer D, Rifat SL (1996) Risk for neuropathologically confirmed Alzheimer’s disease and residual aluminium in municipal drinking water employing weighted residential histories. Neurology 46:401–405

    PubMed  CAS  Google Scholar 

  • Mello NK (1975) Behavioral toxicology: a developing discipline. Fed Proc 34:1832–1834

    PubMed  CAS  Google Scholar 

  • Miu AC, Andreescu CE, Vasiu R, Oleanu AI (2003) A behavioural and histological study of the effects of long-term exposure of adult rats to aluminium. Int J Neurosci 113:1197–1211

    Article  PubMed  Google Scholar 

  • Miu AC, Olteanu AI, Miclea M (2004) A behavioral and ultrastructural dissection of the interference of aluminium with aging. J Alzheimers Dis 6:315–328

    PubMed  CAS  Google Scholar 

  • Monteagudo FSE, Issacson LC, Wilson G, Hickman R, Folb PI (1988) Aluminium excretion by the distal tubule of the pig kidney. Nephron 49:245–250

    Article  PubMed  CAS  Google Scholar 

  • Motoori S, Majima HJ, Ebara M, Kato H, Hirai F, Kakinuma S et al (2001) Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell line HLE. Cancer Res 61:5382–5388

    PubMed  CAS  Google Scholar 

  • Murakami K, Yoshino M (2004) Aluminium decreases the glutathione regeneration by the inhibition of NADP-isocitrate dehydrogenase in mitochondria. J Cell Biochem 93:1267–1271

    Article  PubMed  CAS  Google Scholar 

  • Nayak P (2002) Aluminium: impacts and disease. Environ Res Sect A 89:101–115 Review

    Article  CAS  Google Scholar 

  • Nehru B, Anand P (2005) Oxidative damage following chronic aluminium exposure in adult and pup rat brains. J Trace Elem Med Biol 19:203–208

    PubMed  CAS  Google Scholar 

  • Nehru B, Bhalla P (2006) Reversal of an aluminium induced alteration in redox status in different regions of rat brain by administration of centrophenoxine. Mol Cell Biochem 290:185–191

    Article  PubMed  CAS  Google Scholar 

  • Niemoeller OM, Kiedaisch V, Dreischer P, Wieder T, Lang F (2006) Stimulation of eryptosis by aluminium ions. Toxicol Appl Pharmacol 217:168–175

    Article  PubMed  CAS  Google Scholar 

  • Niu PY, Niu Q, Zhang QL, Wang LP, He SE, Wu TC (2005) Aluminium impairs rat neural cell mitochondria in vitro. Int J Immunopathol Pharmacol 18:683–689

    PubMed  CAS  Google Scholar 

  • Ochmanski W, Barabasz W (2000) Aluminium-occurrence and toxicity for organisms. Przegl Lek 57:665–668

    PubMed  CAS  Google Scholar 

  • Ohman LO, Martin RB (1994) Citrate as the main small molecule binding Al3+ in serum. Clin Chem 40:598–601

    PubMed  CAS  Google Scholar 

  • Ohyashiki T, Suzuki S, Satoh E, Uemori Y (1998) A marked stimulation of Fe2+ initiated lipid peroxidation in phospholipid liposomes by a lipophilic aluminium complex, aluminium acetylacetonate. Biochim Biophys Acta 1389:141–149

    PubMed  CAS  Google Scholar 

  • Ohyashiki T, Satoh E, Okada M, Takadera T, Sahara M (2002) Nerve growth factor protects against aluminium-mediated cell death. Toxicology 176:195–207

    Article  PubMed  CAS  Google Scholar 

  • Parker WD, Parks JK, Filley CM, Kleinschmidt-DeMasters BK (1994) Electron transport defects in Alzheimer’s disease brain. Neurology 44:1090–1096

    PubMed  Google Scholar 

  • Perl DP, Moalem S (2006) Aluminium and Alzheimer’s disease, a personal perspective after 25 years. J Alzheimers Dis 9:291–300

    PubMed  CAS  Google Scholar 

  • Perl DP, Gajdusek DC, Garruto RM (1982) Intraneuronal aluminium accumulation in any itrophic lateral sclerosis and Parkinsonism: dementia of Gaum. Science 217:1053–1055

    Article  PubMed  CAS  Google Scholar 

  • Perry RH (1986) Recent advances in neuropathology. Br Med Bull 42:34–41

    PubMed  CAS  Google Scholar 

  • Polizzi S, Pira E, Ferrara M, Bugiani M, Papaleo A, Albera R, Palmi S (2002) Neurotoxic effects of aluminium among foundry workers and Alzheimer’s disease. Neurotoxicology 23:761–774

    Article  PubMed  CAS  Google Scholar 

  • Prakash NT, Rao KS (1995) Modulations in antioxidant enzymes in different tissues of marine bivalve Perna viridis during heavy metal exposure. Mol Cell Biochem 146:107–113

    Article  PubMed  CAS  Google Scholar 

  • Ratan RR, Barban JM (1995) Apoptotic death in an in vitro model of neuronal oxidative stress. Clin Exp Pharm Phys 22:309–310

    Article  CAS  Google Scholar 

  • Reed DJ (1986) Regulation of reductive process by glutathione. Biol Chem Pharmacol 35:7–13

    CAS  Google Scholar 

  • Reed DJ (2004) Mitochondrial glutathione and chemically induced stress including ethanol. Drug Metab Rev 36:569–582

    Article  PubMed  CAS  Google Scholar 

  • Reiter L (1978) An introduction to neurobehavioral toxicology. Environ Health Perspect 26:5–7

    Article  PubMed  CAS  Google Scholar 

  • Ribes D, Colomina MT, Vicens P, Domingo JL (2008) Effects of oral aluminium exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer’s disease. Exp Neurol 214:293–300

    Article  PubMed  CAS  Google Scholar 

  • Rifat SL, Eastwood MR, McLachlan DR, Corey PN (1990) Effect of exposure of miners to aluminium powder. Lancet 336:1162–1165

    Article  PubMed  CAS  Google Scholar 

  • Riihimäki V, Hänninen H, Akila R, Kovala T, Kuosma E, Paakkulainen H, Valkonen S, Engström B (2000) Body burden of aluminium in relation to central nervous system function among metal inert-gas welders. Scand J Work Environ Health 26:118–130

    PubMed  Google Scholar 

  • Robertson JA, Felsenfeld AJ, Haygood CC, Wilson P, Clarke C, Llach F (1983) Animal model of aluminium-induced osteomalacia: role of chronic renal failure. Kidney Int 23:327–335

    Article  PubMed  CAS  Google Scholar 

  • Roig JL, Fuentes S, Teresa Colomina M, Vicens P, Domingo JL (2006) Aluminium, restraint stress and aging: behavioral effects in rats after 1 and 2 years of aluminium exposure. Toxicology 218:112–124

    Article  PubMed  CAS  Google Scholar 

  • Roy AK, Talukder G, Sharma A (1991) Similar effects in vivo of two aluminium salts on the liver, kidney, bone, and brain of Rattus norvegicus. Bull Environ Contam Toxicol 47:288–295

    Article  PubMed  CAS  Google Scholar 

  • Sahin G, Varol I, Temizer A (1994) Determination of aluminium levels in the kidney, liver, and brain of mice treated with aluminium hydroxide. Biol Trace Element Res 41:129–135

    Article  CAS  Google Scholar 

  • Sánchez-Iglesias S, Soto-Otero R, Iglesias-González J, Barciela-Alonso MC, Bermejo-Barrera P, Méndez-Alvarez E (2007) Analysis of brain regional distribution of aluminium in rats via oral and intraperitoneal administration. J Trace Elem Med Biol 21:31–34

    Article  PubMed  CAS  Google Scholar 

  • Santos F, Chan JCM, Yang MS, Savory J, Wills MR (1987) Aluminium deposition in the central nervous system: Preferential accumulation in the hippocampus in weanling rats. Med Biol 65:53–55

    PubMed  CAS  Google Scholar 

  • Santucci D, Rankin J, Laviola G, Aloe L, Alleva E (1994) Early exposure to aluminium affects eight-arm maze performance and hippocampal nerve growth factor levels in adult mice. Neurosci Lett 166:89–92

    Article  PubMed  CAS  Google Scholar 

  • Savory J, Herman MM, Ghribi O (2003) Intracellular mechanisms underlying aluminium-induced apoptosis in rabbit brain. J Inorg Biochem 97:151–154

    Article  PubMed  CAS  Google Scholar 

  • Schetinger MR, Bonan CD, Morsch VM, Bohrer D, Valentim LM, Rodrigues SR (1999) Effects of aluminium sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice. Braz J Med Biol Res 32:761–766

    Article  PubMed  CAS  Google Scholar 

  • Schreeder MT, Favero MS, Hughes JR, Petersen NJ, Bennett PH, Maynard JE (1983) Dialysis encephalopathy and aluminium exposure: An epidemiologic analysis. J Chron Dis 36:581–593

    Article  PubMed  CAS  Google Scholar 

  • Sedman AB, Wilkening GN, Warady BA, Lum GM, Alfrey AC (1984) Encephalopathy in childhood secondary to aluminium toxicity. J Pediatr 105:836–848

    Article  PubMed  CAS  Google Scholar 

  • Sethi P, Jyoti A, Singh R, Hussain E, Sharma D (2008) Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats. Neurotoxicology 29:1069–1079

    Article  PubMed  CAS  Google Scholar 

  • Shirabe T, Irie K, Uchida M (2002) Autopsy case of aluminium encephalopathy. Neuropathology 22:206–210

    Article  PubMed  Google Scholar 

  • Sjögren B, Iregren A, Frech W, Hagman M, Johansson L, Tesarz M, Wennberg A (1996) Effects on the nervous system among welders exposed to aluminium and manganese. Occup Environ Med 53:32–40

    Article  PubMed  Google Scholar 

  • Somova LI, Missankov A, Khan M (1997) Chronic aluminium intoxication in rats: dose-dependent morphological changes. Methods Find Exp Clin Pharmacol 19:599–604

    PubMed  CAS  Google Scholar 

  • Strong MJ, Garruto RM, Joshi JG, Mundy WR, Shafer TJ (1996) Can the mechanisms of aluminium neurotoxicity be integrated into a unified scheme? J Toxicol Environ Health 48:599–613

    Article  PubMed  CAS  Google Scholar 

  • Swain C, Chainy GB (1998) Effects of aluminium sulphate and citric acid ingestion on lipid peroxidation and on activities of superoxide dismutase and catalase in cerebral hemisphere and liver of developing young chicks. Mol Cell Biochem 187:163–172

    Article  PubMed  CAS  Google Scholar 

  • 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 112:27–42

    Article  PubMed  CAS  Google Scholar 

  • Szilagyi M, Bokori J, Fekete S, Vetesi F, Albert M, Kadar I (1994) Effects of long-term aluminium exposure on certain serum constituents in broiler chickens. Eur J Clin Chem Clin Biochem 32:485–496

    PubMed  CAS  Google Scholar 

  • Takeyama N, Matsuo N, Tanaka T (1993) Oxidative damage to mitochondria is mediated by the Ca2+ dependent inner-membrane permeability transition. Biochem J 294:719–725

    PubMed  CAS  Google Scholar 

  • Thorne BM, Donohoe T, Lin K, Lyon S, Mediros DM, Weaver HL (1986) Aluminium ingestion and behaviour in the Long-Evans rat. Physiol Behav 36:63–67

    Article  PubMed  CAS  Google Scholar 

  • Tilson HA (1993) Neurobehavioral methods used in neurotoxicological research. Toxicol Lett 68:231–240

    Article  PubMed  CAS  Google Scholar 

  • Tilson HA, Mitchell CL (1984) Neurobehavioral techniques to assess the effects of chemicals on the nervous system. Annu Rev Pharmacol Toxicol 24:425–450

    Article  PubMed  CAS  Google Scholar 

  • Tipton IH, Cook MJ (1963) Trace elements in human tissue. Part II. Adult subjects from the United States. Health Phys 9:103–145

    Article  PubMed  CAS  Google Scholar 

  • Touam M, Martinez F, Lacour B, Bourdon R, Zingraff J, Di Giulio S, Drueke T (1983) Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies. Clin Nephrol 19:295–298

    PubMed  CAS  Google Scholar 

  • Trapp GA (1983) Plasma aluminium is bound to transferin. Life Sci 33:311–316

    Article  PubMed  CAS  Google Scholar 

  • Tuneva J, Chittur S, Boldyrev AA, Birman I, Carpenter DO (2006) Cerebellar granule cell death induced by aluminium. Neurotox Res 9:297–304

    Article  PubMed  CAS  Google Scholar 

  • Van der Voet GB, De Wolff FA (1987) The effect of di- and trivalent iron on the intestinal absorption of aluminium in rats. Toxicol Appl Pharmacol 90:190–197

    Article  PubMed  Google Scholar 

  • Walton JR (2006) Aluminium in hippocampal neurons from humans with Alzheimer’s disease. NeuroToxicol 27:385–394

    Article  CAS  Google Scholar 

  • Walton JR (2007) An aluminium-based rat model for Alzheimer disease exhibits oxidative damage, inhibition of PP2A activity, hyperphosphorylated tau and granulovascuolar degeneration. J Inorg Biochem 101:1275–1284

    Article  PubMed  CAS  Google Scholar 

  • Wilhelm M, Sprenger KBG, Vossas V, Ohnesorge FK (1987) Aluminium load in chronic plasma exchange. Clin Toxicol 25:209–220

    Article  CAS  Google Scholar 

  • Williams RJP (1996) Aluminium and biological systems: an introduction. Coord Chem Rev 149:1–9

    CAS  Google Scholar 

  • Williams JW, Vera SR, Peters TG (1966) Biliary excretion of aluminium in aluminium osteodystrophy with liver diseases. Ann Int Med 104:781–785

    Google Scholar 

  • Williams JW, Vera SR, Peters TG, Luther RW, Bhattacharya S, Spears H, Graham A, Pitcock JA, Crawford AJ, Palmieri GM (1986) Biliary excretion of aluminium in aluminium osteodystrophy with liver disease. Ann Intern Med 104:782–785

    PubMed  CAS  Google Scholar 

  • Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem 273:28510–28515

    Article  PubMed  CAS  Google Scholar 

  • Wills MR, Hewitt CD, Sturgill BC, Savory J, Herman MM (1993) Long-term oral or intravenous aluminium administration in rabbits. I. Renal and hepatic changes. Ann Clin Lab Sci 23:1–16

    PubMed  CAS  Google Scholar 

  • Wisniewski HM (1991) About the association of aluminium and Alzheimer’s disease: a commentary. In: Nicolini M, Zatta PF, Corain B (eds) Aluminium in chemistry, biology and medicine. Cortina International, Verona, pp 115–117

    Google Scholar 

  • Woodson GC (1998) An interesting case of osteomalacia due to antacid use associated with stainable bone aluminium in a patient with normal renal function. Bone 22:695–698

    Article  PubMed  CAS  Google Scholar 

  • Xiong Y, Shie FS, Zhang J, Lee CP, Ho YS (2005) Prevention of mitochondrial dysfunction in post-traumatic mouse brain by superoxide dismutase. J Neurochem 95:732–744

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA (1987) Toxicity of aluminium exposure to the neonatal and immature rabbit. Fundam Appl Toxicol 9:795–806

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA (2000) The toxicology of aluminium in the brain: a review. Neurotoxicology 2000(21):813–828

    Google Scholar 

  • Yokel RA (2002) Brain uptake, retention, and efflux of aluminium and manganese. Environ Health Perspect 110:699–704

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA (2006) Blood-brain barrier flux of aluminium, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis 10:223–253 Review

    PubMed  Google Scholar 

  • Yokel RA, McNamara PJ (1985) Aluminium bioavailability and disposition in adult and immature rabbits. Toxicol Appl Pharmacol 77:344–352

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA, McNamara PJ (2001) Aluminium toxicokinetics: an updated minireview. Pharmacol Toxicol 88:159–167

    Article  PubMed  CAS  Google Scholar 

  • Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y (1997) An immunohistochemical study on manganese superoxide dismutase in Parkinson’s disease. J Neurol Sci 148:181–186

    Article  PubMed  CAS  Google Scholar 

  • Zaman K, Zaman A, Batcabe J (1993) Hematological effects of aluminium on living organisms. Comp Biochem Physiol C 106:285–293

    Article  PubMed  CAS  Google Scholar 

  • Zatta P, Ibn-Lkhayat-Idrissi M, Zambenedetti P, Kilyen M, Kiss T (2002a) In vivo and in vitro effects of aluminium on the activity of mouse brain acetylcholinesterase. Brain Res Bull 59:41–45

    Article  PubMed  CAS  Google Scholar 

  • Zatta P, Kiss T, Suwalsky M, Berthon G (2002b) Aluminium(III) as a promoter of cellular oxidation. Coord Chem Rev 228:271–284

    Article  CAS  Google Scholar 

  • Zhang K, Zhou Q (2005) Toxic effects of Al-based coagulants on Brassica chinensis and Raphanus sativus growing in acid and neutral conditions. Environ Toxicol 20:179–187

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJA (1990) The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 265:16330–16336

    PubMed  CAS  Google Scholar 

  • Ziegler DM (1985) Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Annu Rev Biochem 54:305–329

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kiran Dip Gill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, V., Gill, K.D. Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Arch Toxicol 83, 965–978 (2009). https://doi.org/10.1007/s00204-009-0455-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-009-0455-6

Keywords

Navigation