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Aluminium and lead: molecular mechanisms of brain toxicity

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Abstract

The fact that aluminium (Al) and lead (Pb) are both toxic metals to living organisms, including human beings, was discovered a long time ago. Even when Al and Pb can reach and accumulate in almost every organ in the human body, the central nervous system is a particular target of the deleterious effects of both metals. Select human population can be at risk of Al neurotoxicity, and Al is proposed to be involved in the etiology of neurodegenerative diseases. Pb is a widespread environmental hazard, and the neurotoxic effects of Pb are a major public health concern. In spite of the numerous efforts and the accumulating evidence in this area of research, the mechanisms of Al and Pb neurotoxicity are still not completely elucidated. This review will particularly address the involvement of oxidative stress, membrane biophysics alterations, deregulation of cell signaling, and the impairment of neurotransmission as key aspects involved Al and Pb neurotoxicity.

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References

  • Abramov AY, Jacobson J, Wientjes F, Hothersall J, Canevari L, Duchen MR (2005) Expression and modulation of an NADPH oxidase in mammalian astrocytes. J Neurosci 25:9176–9184

    PubMed  CAS  Google Scholar 

  • Adonaylo VN, Oteiza PI (1999a) Lead intoxication: antioxidant defenses and oxidative damage in rat brain. Toxicology 135:77–85

    PubMed  CAS  Google Scholar 

  • Adonaylo VN, Oteiza PI (1999b) Pb2+ promotes lipid oxidation and alterations in membrane physical properties. Toxicology 132:19–32

    PubMed  CAS  Google Scholar 

  • Ahamed M, Siddiqui MK (2007) Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta 383:57–64

    PubMed  CAS  Google Scholar 

  • Aimo L, Oteiza PI (2006) Zinc deficiency increases the susceptibility of human neuroblastoma cells to lead-induced activator protein-1 activation. Toxicol Sci 91:184–191

    PubMed  CAS  Google Scholar 

  • Alfano DP, Petit TL, LeBoutillier JC (1983) Development and plasticity of the hippocampal-cholinergic system in normal and early lead exposed rats. Brain Res 312:117–124

    PubMed  CAS  Google Scholar 

  • Alfrey AC, LeGendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 294:184–188

    PubMed  CAS  Google Scholar 

  • Andrasi E, Pali N, Molnar Z, Kosel S (2005) Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis 7:273–284

    PubMed  CAS  Google Scholar 

  • Aremu DA, Meshitsuka S (2005) Accumulation of aluminum by primary cultured astrocytes from aluminum amino acid complex and its apoptotic effect. Brain Res 1031:284–296

    PubMed  CAS  Google Scholar 

  • Aruoma OI, Halliwell B, Laughton MJ, Quinlan GJ, Gutteridge JM (1989) The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron(II)–iron(III) complex. Biochem J 258:617–620

    PubMed  CAS  Google Scholar 

  • Bechara EJ (1996) Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinic acid. Braz J Med Biol Res 29:841–851

    PubMed  CAS  Google Scholar 

  • Bielarczyk H, Tian X, Suszkiw JB (1996) Cholinergic denervation-like changes in rat hippocampus following developmental lead exposure. Brain Res 708:108–115

    PubMed  CAS  Google Scholar 

  • Bielarczyk H, Tomaszewicz M, Szutowicz A (1998) Effect of aluminum on acetyl-CoA and acetylcholine metabolism in nerve terminals. J Neurochem 70:1175–1181

    PubMed  CAS  Google Scholar 

  • Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna S, Bettaiya R (2008) Lead-induced increase in antioxidant enzymes and lipid peroxidation products in developing rat brain. Biometals 21:9–16

    PubMed  CAS  Google Scholar 

  • Braga MF, Pereira EF, Marchioro M, Albuquerque EX (1999) Lead increases tetrodotoxin-insensitive spontaneous release of glutamate and GABA from hippocampal neurons. Brain Res 826:10–21

    PubMed  CAS  Google Scholar 

  • Bressler J, Kim KA, Chakraborti T, Goldstein G (1999) Molecular mechanisms of lead neurotoxicity. Neurochem Res 24:595–600

    PubMed  CAS  Google Scholar 

  • Campbell A, Yang EY, Tsai-Turton M, Bondy SC (2002) Pro-inflammatory effects of aluminum in human glioblastoma cells. Brain Res 933:60–65

    PubMed  CAS  Google Scholar 

  • Canfield RL, Henderson CR Jr, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP (2003) Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 348:1517–1526

    PubMed  CAS  Google Scholar 

  • DC C (2000) Blood lead levels in young children—United States and selected states, 1996–1999. MMWR Morb Mortal Wkly Rep 49:1133–1137

    Google Scholar 

  • Cordeiro JM, Silva VS, Oliveira CR, Goncalves PP (2003) Aluminium-induced impairment of Ca2+ modulatory action on GABA transport in brain cortex nerve terminals. J Inorg Biochem 97:132–142

    PubMed  CAS  Google Scholar 

  • Cory-Slechta DA, Pokora MJ, Widzowski DV (1992) Postnatal lead exposure induces supersensitivity to the stimulus properties of a D2–D3 agonist. Brain Res 598:162–172

    PubMed  CAS  Google Scholar 

  • Costa CA, Trivelato GC, Pinto AM, Bechara EJ (1997) Correlation between plasma 5-aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers. Clin Chem 43:1196–1202

    PubMed  CAS  Google Scholar 

  • Chakraborti T, Kim KA, Goldstein GG, Bressler JP (1999) Increased AP-1 DNA binding activity in PC12 cells treated with lead. J Neurochem 73:187–194

    PubMed  CAS  Google Scholar 

  • Chen L, Yang X, Jiao H, Zhao B (2002) Tea catechins protect against lead-induced cytotoxicity, lipid peroxidation, and membrane fluidity in HepG2 cells. Toxicol Sci 69:149–156

    PubMed  CAS  Google Scholar 

  • Chetty CS, Reddy GR, Murthy KS, Johnson J, Sajwan K, Desaiah D (2001) Perinatal lead exposure alters the expression of neuronal nitric oxide synthase in rat brain. Int J Toxicol 20:113–120

    PubMed  CAS  Google Scholar 

  • Dabrowska-Bouta B, Struzynska L, Walski M, Rafalowska U (2008) Myelin glycoproteins targeted by lead in the rodent model of prolonged exposure. Food Chem Toxicol 46:961–966

    PubMed  CAS  Google Scholar 

  • Dabrowska-Bouta B, Sulkowski G, Bartosz G, Walski M, Rafalowska U (1999) Chronic lead intoxication affects the myelin membrane status in the central nervous system of adult rats. J Mol Neurosci 13:127–139

    PubMed  CAS  Google Scholar 

  • Devi CB, Reddy GH, Prasanthi RP, Chetty CS, Reddy GR (2005) Developmental lead exposure alters mitochondrial monoamine oxidase and synaptosomal catecholamine levels in rat brain. Int J Dev Neurosci 23:375–381

    PubMed  CAS  Google Scholar 

  • Devi SS, Biswas AR, Biswas RA, Vinayagamoorthy N, Krishnamurthi K, Shinde VM, Hengstler JG, Hermes M, Chakrabarti T (2007) Heavy metal status and oxidative stress in diesel engine tuning workers of central Indian population. J Occup Environ Med 49:1228–1234

    Article  PubMed  CAS  Google Scholar 

  • Di J, Bi S (2003a) Aluminum ions accelerated the oxidative stress of copper-mediated melanin formation. Spectrochim Acta A Mol Biomol Spectrosc 59:3075–3083

    PubMed  Google Scholar 

  • Di J, Bi S (2003b) Effect of aluminum (III) on the conversion of dopachrome in the melanin synthesis pathway. Spectrochim Acta A Mol Biomol Spectrosc 59:1689–1696

    PubMed  Google Scholar 

  • Di J, Bi S (2004) Aluminum facilitation of the iron-mediated oxidation of DOPA to melanin. Anal Sci 20:629–634

    PubMed  CAS  Google Scholar 

  • Diaz RS, Monreal J (1995) Protein-independent lead permeation through myelin lipid liposomes. Mol Pharmacol 47:766–771

    PubMed  CAS  Google Scholar 

  • Dousset N, Ferretti G, Galeazzi T, Taus M, Gouaze V, Berthon G, Curatola G (1997) Effect of aluminium ions on liposomal membranes as detected by Laurdan fluorescence. Free Radic Res 27:291–299

    PubMed  CAS  Google Scholar 

  • Drago D, Bettella M, Bolognin S, Cendron L, Scancar J, Milacic R, Ricchelli F, Casini A, Messori L, Tognon G, Zatta P (2008) Potential pathogenic role of beta-amyloid(1–42)-aluminum complex in Alzheimer’s disease. Int J Biochem Cell Biol 40:731–746

    PubMed  CAS  Google Scholar 

  • Dubas TC, Hrdina PD (1978) Behavioural and neurochemical consequences of neonatal exposure to lead in rats. J Environ Pathol Toxicol 2:471–484

    PubMed  CAS  Google Scholar 

  • El-Rahman SS (2003) Neuropathology of aluminum toxicity in rats (glutamate and GABA impairment). Pharmacol Res 47:189–194

    PubMed  CAS  Google Scholar 

  • Engle MJ, Volpe JJ (1990) Glutamine synthetase activity of developing astrocytes is inhibited in vitro by very low concentrations of lead. Brain Res Dev Brain Res 55:283–287

    PubMed  CAS  Google Scholar 

  • Exley C (1998) Does antiperspirant use increase the risk of aluminium-related disease, including Alzheimer’s disease? Mol Med Today 4:107–109

    PubMed  CAS  Google Scholar 

  • Exley C (2004a) Aluminum in antiperspirants: more than just skin deep. Am J Med 117:969–970

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Fahn S (2003) Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 991:1–14

    PubMed  CAS  Google Scholar 

  • Fu HJ, Hu QS, Lin ZN, Ren TL, Song H, Cai CK, Dong SZ (2003) Aluminum-induced apoptosis in cultured cortical neurons and its effect on SAPK/JNK signal transduction pathway. Brain Res 980:11–23

    PubMed  CAS  Google Scholar 

  • Ganrot PO (1986) Metabolism and possible health effects of aluminum. Environ Health Perspect 65:363–441

    PubMed  CAS  Google Scholar 

  • Garcon G, Leleu B, Zerimech F, Marez T, Haguenoer JM, Furon D, Shirali P (2004) Biologic markers of oxidative stress and nephrotoxicity as studied in biomonitoring of adverse effects of occupational exposure to lead and cadmium. J Occup Environ Med 46:1180–1186

    PubMed  CAS  Google Scholar 

  • Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336:385–388

    PubMed  CAS  Google Scholar 

  • Garza A, Vega R, Soto E (2006) Cellular mechanisms of lead neurotoxicity. Med Sci Monit 12:RA57–RA65

    PubMed  Google Scholar 

  • Gedeon Y, Ramesh GT, Wellman PJ, Jadhav AL (2001) Changes in mesocorticolimbic dopamine and D1/D2 receptor levels after low level lead exposure: a time course study. Toxicol Lett 123:217–226

    PubMed  CAS  Google Scholar 

  • Ghribi O, Herman MM, DeWitt DA, Forbes MS, Savory J (2001a) Abeta(1–42) and aluminum induce stress in the endoplasmic reticulum in rabbit hippocampus, involving nuclear translocation of gadd 153 and NF-kappaB. Brain Res Mol Brain Res 96:30–38

    PubMed  CAS  Google Scholar 

  • Ghribi O, Herman MM, Forbes MS, DeWitt DA, Savory J (2001b) GDNF protects against aluminum-induced apoptosis in rabbits by upregulating Bcl-2 and Bcl-XL and inhibiting mitochondrial Bax translocation. Neurobiol Dis 8:764–773

    PubMed  CAS  Google Scholar 

  • Gill KD, Gupta V, Sandhir R (2003) Ca2+/calmodulin-mediated neurotransmitter release and neurobehavioural deficits following lead exposure. Cell Biochem Funct 21:345–353

    PubMed  CAS  Google Scholar 

  • Godwin HA (2001) The biological chemistry of lead. Curr Opin Chem Biol 5:223–227

    PubMed  CAS  Google Scholar 

  • Golub MS, Han B, Keen CL (1999) Aluminum uptake and effects on transferrin mediated iron uptake in primary cultures of rat neurons, astrocytes and oligodendrocytes. Neurotoxicology 20:961–970

    PubMed  CAS  Google Scholar 

  • Golub MS, Zhang W, Keen CL, Goldkorn T (2002) Cellular actions of Al at low (1.25 microM) concentrations in primary oligodendrocyte culture. Brain Res 941:82–90

    PubMed  CAS  Google Scholar 

  • Gonçalves PP, Silva VS (2007) Does neurotransmission impairment accompany aluminium neurotoxicity? J Inorg Biochem 101:1291–1338

    PubMed  Google Scholar 

  • Goyer RA (1996) Results of lead research: prenatal exposure and neurological consequences. Environ Health Perspect 104:1050–1054

    PubMed  CAS  Google Scholar 

  • Guilarte TR, McGlothan JL (2003) Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb2+-exposed rats: implications for synaptic targeting and cell surface expression of NMDAR complexes. Brain Res Mol Brain Res 113:37–43

    PubMed  CAS  Google Scholar 

  • Guilarte TR, McGlothan JL, Nihei MK (2000) Hippocampal expression of N-methyl-d-aspartate receptor (NMDAR1) subunit splice variant mRNA is altered by developmental exposure to Pb(2+). Brain Res Mol Brain Res 76:299–305

    PubMed  CAS  Google Scholar 

  • Gulson BL, Pounds JG, Mushak P, Thomas BJ, Gray B, Korsch MJ (1999) Estimation of cumulative lead releases (lead flux) from the maternal skeleton during pregnancy and lactation. J Lab Clin Med 134:631–640

    PubMed  CAS  Google Scholar 

  • Gurer H, Ercal N (2000) Can antioxidants be beneficial in the treatment of lead poisoning? Free Radic Biol Med 29:927–945

    PubMed  CAS  Google Scholar 

  • Gutteridge JM, Quinlan GJ, Clark I, Halliwell B (1985) Aluminium salts accelerate peroxidation of membrane lipids stimulated by iron salts. Biochim Biophys Acta 835:441–447

    PubMed  CAS  Google Scholar 

  • Habermann E, Crowell K, Janicki P (1983) Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol 54:61–70

    PubMed  CAS  Google Scholar 

  • Hanas JS, Rodgers JS, Bantle JA, Cheng YG (1999) Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins. Mol Pharmacol 56:982–988

    PubMed  CAS  Google Scholar 

  • Hortnagl H, Potter PE, Hanin I (1987) Effect of cholinergic deficit induced by ethylcholine aziridinium on serotonergic parameters in rat brain. Neuroscience 22:203–213

    PubMed  CAS  Google Scholar 

  • Huang M, Krepkiy D, Hu W, Petering DH (2004) Zn-, Cd-, and Pb-transcription factor IIIA: properties, DNA binding, and comparison with TFIIIA-finger 3 metal complexes. J Inorg Biochem 98:775–785

    PubMed  CAS  Google Scholar 

  • Ittel TH (1993) Determinants of gastrointestinal absorption and distribution of aluminium in health and uraemia. Nephrol Dial Transplant 8:17–24

    PubMed  Google Scholar 

  • Jankowska A, Madziar B, Tomaszewicz M, Szutowicz A (2000) Acute and chronic effects of aluminum on acetyl-CoA and acetylcholine metabolism in differentiated and nondifferentiated SN56 cholinergic cells. J Neurosci Res 62:615–622

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Johnson VJ, Sharma RP (2003) Aluminum disrupts the pro-inflammatory cytokine/neurotrophin balance in primary brain rotation-mediated aggregate cultures: possible role in neurodegeneration. Neurotoxicology 24:261–268

    PubMed  CAS  Google Scholar 

  • Julka D, Gill KD (1996) Altered calcium homeostasis: a possible mechanisms of aluminium-induced neurotoxicity. Biochim Biophys Acta 1315:47–54

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kala SV, Jadhav AL (1995) Region-specific alterations in dopamine and serotonin metabolism in brains of rats exposed to low levels of lead. Neurotoxicology 16:297–308

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kern M, Wisniewski M, Cabell L, Audesirk G (2000) Inorganic lead and calcium interact positively in activation of calmodulin. Neurotoxicology 21:353–363

    PubMed  CAS  Google Scholar 

  • Kim KA, Chakraborti T, Goldstein G, Johnston M, Bressler J (2002) Exposure to lead elevates induction of zif268 and Arc mRNA in rats after electroconvulsive shock: the involvement of protein kinase C. J Neurosci Res 69:268–277

    PubMed  CAS  Google Scholar 

  • Kim KA, Chakraborti T, Goldstein GW, Bressler JP (2000) Immediate early gene expression in PC12 cells exposed to lead: requirement for protein kinase C. J Neurochem 74:1140–1146

    PubMed  CAS  Google Scholar 

  • Kim S, Nam J, Kim K (2007) Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain. Hum Exp Toxicol 26:741–746

    PubMed  CAS  Google Scholar 

  • Klaassen CD (2001) Heavy metals and heavy-metal antagonists. In: Hardman JG, Limbird LE, Goodman Gilman A (eds) The pharmacological basis of therapeutics. McGraw Hill, New York, pp 1851–1875

  • Krewski D, Yokel RA, Nieboer E, Borchelt D, Cohen J, Harry J, Kacew S, Lindsay J, Mahfouz AM, Rondeau V (2007) Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide. J Toxicol Environ Health B Crit Rev 10(Suppl 1):1–269

    PubMed  CAS  Google Scholar 

  • Kumar S (2002) Aluminium-induced changes in the rat brain serotonin system. Food Chem Toxicol 40:1875–1880

    PubMed  CAS  Google Scholar 

  • Kursula P, Majava V (2007) A structural insight into lead neurotoxicity and calmodulin activation by heavy metals. Acta Crystallogr Sect F Struct Biol Cryst Commun 63:653–656

    PubMed  Google Scholar 

  • Lanphear BP, Dietrich K, Auinger P, Cox C (2000) Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents. Public Health Rep 115:521–529

    PubMed  CAS  Google Scholar 

  • Leret ML, Garcia-Uceda F, Antonio MT (2002) Effects of maternal lead administration on monoaminergic, GABAergic and glutamatergic systems. Brain Res Bull 58:469–473

    PubMed  CAS  Google Scholar 

  • Levesque L, Mizzen CA, McLachlan DR, Fraser PE (2000) Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes. Brain Res 877:191–202

    PubMed  CAS  Google Scholar 

  • Li PJ, Sheng YZ, Wang QY, Gu LY, Wang YL (2000) Transfer of lead via placenta and breast milk in human. Biomed Environ Sci 13:85–89

    PubMed  CAS  Google Scholar 

  • Lidsky TI, Schneider JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19

    PubMed  Google Scholar 

  • Loikkanen J, Naarala J, Vahakangas KH, Savolainen KM (2003) Glutamate increases toxicity of inorganic lead in GT1–7 neurons: partial protection induced by flunarizine. Arch Toxicol 77:663–671

    PubMed  CAS  Google Scholar 

  • Long GJ, Rosen JF, Schanne FA (1994) Lead activation of protein kinase C from rat brain. Determination of free calcium, lead, and zinc by 19F NMR. J Biol Chem 269:834–837

    PubMed  CAS  Google Scholar 

  • Lukiw WJ, Percy ME, Kruck TP (2005) Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in human brain cells in primary culture. J Inorg Biochem 99:1895–1898

    PubMed  CAS  Google Scholar 

  • Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA (2005) Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc 127:9495–9505

    PubMed  CAS  Google Scholar 

  • Mailloux RJ, Appanna VD (2007) Aluminum toxicity triggers the nuclear translocation of HIF-1alpha and promotes anaerobiosis in hepatocytes. Toxicol In Vitro 21:16–24

    PubMed  CAS  Google Scholar 

  • Marchetti C (2003) Molecular targets of lead in brain neurotoxicity. Neurotox Res 5:221–236

    PubMed  Google Scholar 

  • Markovac J, Goldstein GW (1988) Picomolar concentrations of lead stimulate brain protein kinase C. Nature 334:71–73

    PubMed  CAS  Google Scholar 

  • McDonald LJ, Mamrack MD (1988) Aluminum affects phosphoinositide hydrolysis by phosphoinositidase C. Biochem Biophys Res Commun 155:203–208

    PubMed  CAS  Google Scholar 

  • McDonald LJ, Mamrack MD (1995) Phosphoinositide hydrolysis by phospholipase C modulated by multivalent cations La(3+), Al(3+), neomycin, polyamines, and melittin. J Lipid Mediat Cell Signal 11:81–91

    PubMed  CAS  Google Scholar 

  • McIntosh MJ, Meredith PA, Moore MR, Goldberg A (1989) Action of lead on neurotransmission in rats. Xenobiotica 19:101–113

    Article  PubMed  CAS  Google Scholar 

  • Meglio L, Oteiza PI (1999) Aluminum enhances melanin-induced lipid peroxidation. Neurochem Res 24:1001–1008

    PubMed  CAS  Google Scholar 

  • Mendez-Alvarez E, Soto-Otero R, Hermida-Ameijeiras A, Lopez-Real AM, Labandeira-Garcia JL (2002) Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson’s disease. Biochim Biophys Acta 1586:155–168

    PubMed  CAS  Google Scholar 

  • Milanese M, Lkhayat MI, Zatta P (2001) Inhibitory effect of aluminum on dopamine beta-hydroxylase from bovine adrenal gland. J Trace Elem Med Biol 15:139–141

    PubMed  CAS  Google Scholar 

  • Naarala JT, Loikkanen JJ, Ruotsalainen MH, Savolainen KM (1995) Lead amplifies glutamate-induced oxidative stress. Free Radic Biol Med 19:689–693

    PubMed  CAS  Google Scholar 

  • Nayak P, Chatterjee AK (2003) Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain. BMC Neurosci 4:4

    PubMed  Google Scholar 

  • Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR (2000) N-methyl-d-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning. Neuroscience 99:233–242

    PubMed  CAS  Google Scholar 

  • Nostrandt AC, Shafer TJ, Mundy WR, Padilla S (1996) Inhibition of rat brain phosphatidylinositol-specific phospholipase C by aluminum: regional differences, interactions with aluminum salts, and mechanisms. Toxicol Appl Pharmacol 136:118–125

    PubMed  CAS  Google Scholar 

  • Ohba S, Hiramatsu M, Edamatsu R, Mori I, Mori A (1994) Metal ions affect neuronal membrane fluidity of rat cerebral cortex. Neurochem Res 19:237–241

    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 aluminum complex, aluminum acetylacetonate. Biochim Biophys Acta 1389:141–149

    PubMed  CAS  Google Scholar 

  • Oteiza PI (1994) A mechanism for the stimulatory effect of aluminum on iron-induced lipid peroxidation. Arch Biochem Biophys 308:374–379

    PubMed  Google Scholar 

  • Pandya JD, Dave KR, Katyare SS (2004) Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin. Lipids Health Dis 3:13

    PubMed  Google Scholar 

  • Pennypacker KR, Xiao Y, Xu RH, Harry GJ (1997) Lead-induced developmental changes in AP-1 DNA binding in rat brain. Int J Dev Neurosci 15:321–328

    PubMed  CAS  Google Scholar 

  • Perl DP, Good PF (1987) Uptake of aluminium into central nervous system along nasal-olfactory pathways. Lancet 1:1028

    PubMed  CAS  Google Scholar 

  • Ramesh GT, Manna SK, Aggarwal BB, Jadhav AL (1999) Lead activates nuclear transcription factor-kappaB, activator protein-1, and amino-terminal c-Jun kinase in pheochromocytoma cells. Toxicol Appl Pharmacol 155:280–286

    PubMed  CAS  Google Scholar 

  • Ramesh GT, Manna SK, Aggarwal BB, Jadhav AL (2001) Lead exposure activates nuclear factor kappa B, activator protein-1, c-Jun N-terminal kinase and caspases in the rat brain. Toxicol Lett 123:195–207

    PubMed  CAS  Google Scholar 

  • Ravi SM, Prabhu BM, Raju TR, Bindu PN (2000) Long-term effects of postnatal aluminium exposure on acetylcholinesterase activity and biogenic amine neurotransmitters in rat brain. Indian J Physiol Pharmacol 44:473–478

    PubMed  CAS  Google Scholar 

  • Roberts E (1986) Alzheimer’s disease may begin in the nose and may be caused by aluminosilicates. Neurobiol Aging 7:561–567

    PubMed  CAS  Google Scholar 

  • Ruff HA, Markowitz ME, Bijur PE, Rosen JF (1996) Relationships among blood lead levels, iron deficiency, and cognitive development in two-year-old children. Environ Health Perspect 104:180–185

    PubMed  CAS  Google Scholar 

  • Saimi Y, Kung C (2002) Calmodulin as an ion channel subunit. Annu Rev Physiol 64:289–311

    PubMed  CAS  Google Scholar 

  • Sandhir R, Gill KD (1994) Lead perturbs calmodulin dependent cyclic AMP metabolism in rat central nervous system. Biochem Mol Biol Int 33:729–742

    PubMed  CAS  Google Scholar 

  • Savory J, Huang Y, Wills MR, Herman MM (1998) Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: implications for clinical trials in Alzheimer’s disease. Neurotoxicology 19:209–214

    PubMed  CAS  Google Scholar 

  • Shafer TJ, Mundy WR (1995) Effects of aluminum on neuronal signal transduction: mechanisms underlying disruption of phosphoinositide hydrolysis. Gen Pharmacol 26:889–895

    PubMed  CAS  Google Scholar 

  • Sidhu P, Nehru B (2003) Relationship between lead-induced biochemical and behavioral changes with trace element concentrations in rat brain. Biol Trace Elem Res 92:245–256

    PubMed  CAS  Google Scholar 

  • Sies H, Jones D (2007) Oxidative Stress. In: Fink G (ed) Encyclopedia of stress. Elsevier, San Diego, pp 45–48

    Google Scholar 

  • Silva VS, Cordeiro JM, Matos MJ, Oliveira CR, Goncalves PP (2002) Aluminum accumulation and membrane fluidity alteration in synaptosomes isolated from rat brain cortex following aluminum ingestion: effect of cholesterol. Neurosci Res 44:181–193

    PubMed  CAS  Google Scholar 

  • Strömberg U, Lundh T, Skerfving S (2008) Yearly measurements of blood lead in Swedish children since 1978: the declining trend continues in the petrol-lead-free period 1995–2007. Environ Res 107:332–335

    PubMed  Google Scholar 

  • Toscano CD, Guilarte TR (2005) Lead neurotoxicity: from exposure to molecular effects. Brain Res Brain Res Rev 49:529–554

    PubMed  CAS  Google Scholar 

  • Tsunoda M, Sharma RP (1999) Altered dopamine turnover in murine hypothalamus after low-dose continuous oral administration of aluminum. J Trace Elem Med Biol 13:224–231

    PubMed  CAS  Google Scholar 

  • Uversky VN, Li J, Fink AL (2001) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson’s disease and heavy metal exposure. J Biol Chem 276:44284–44296

    PubMed  CAS  Google Scholar 

  • Valentino M, Fiorini RM, Curatola G, Governa M (1982) Changes of membrane fluidity in erythrocytes of lead-exposed workers. Int Arch Occup Environ Health 51:105–112

    PubMed  CAS  Google Scholar 

  • Verina T, Rohde CA, Guilarte TR (2007) Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. Neuroscience 145:1037–1047

    PubMed  CAS  Google Scholar 

  • Verstraeten SV (2000) Mechanisms involved in the oxidative damage to membranes mediated by aluminum and aluminum-related cations. Effects in vitro and in vivo. In: School of Pharmacy and Biochemistry. University of Buenos Aires, Buenos Aires, Argentina

  • Verstraeten SV, Erlejman AG, Zago MP, Oteiza PI (2002) Aluminum affects membrane physical properties in human neuroblastoma (IMR-32) cells both before and after differentiation. Arch Biochem Biophys 399:167–173

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Golub MS, Keen CL, Oteiza PI (1997a) Myelin is a preferential target of aluminum-mediated oxidative damage. Arch Biochem Biophys 344:289–294

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Keen CL, Golub MS, Oteiza PI (1998) Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids. Biochem J 333:833–838

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Nogueira LV, Schreier S, Oteiza PI (1997b) Effect of trivalent metal ions on phase separation and membrane lipid packing: role in lipid peroxidation. Arch Biochem Biophys 338:121–127

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Oteiza PI (1995) Sc3+, Ga3+, In3+, Y3+, and Be2+ promote changes in membrane physical properties and facilitate Fe2+-initiated lipid peroxidation. Arch Biochem Biophys 322:284–290

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Oteiza PI (2000) Effects of Al3+ and related metals on membrane phase state and hydration: correlation with lipid oxidation. Arch Biochem Biophys 375:340–346

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Oteiza PI (2002) Al3+-mediated changes in membrane physical properties participate in the inhibition of polyphosphoinositide hydrolysis. Arch Biochem Biophys 408:263–271

    PubMed  CAS  Google Scholar 

  • Verstraeten SV, Villaverde MS, Oteiza PI (2003) Al3+-mediated changes on membrane fluidity affects the activity of PI-PLC but not of PLC. Chem Phys Lipids 122:159–163

    PubMed  CAS  Google Scholar 

  • Villeda-Hernandez J, Barroso-Moguel R, Mendez-Armenta M, Nava-Ruiz C, Huerta-Romero R, Rios C (2001) Enhanced brain regional lipid peroxidation in developing rats exposed to low level lead acetate. Brain Res Bull 55:247–251

    PubMed  CAS  Google Scholar 

  • Westerink RH, Vijverberg HP (2002) Ca2+-independent vesicular catecholamine release in PC12 cells by nanomolar concentrations of Pb2+. J Neurochem 80:861–873

    PubMed  CAS  Google Scholar 

  • White LD, Cory-Slechta DA, Gilbert ME, Tiffany-Castiglioni E, Zawia NH, Virgolini M, Rossi-George A, Lasley SM, Qian YC, Basha MR (2007) New and evolving concepts in the neurotoxicology of lead. Toxicol Appl Pharmacol 225:1–27

    PubMed  CAS  Google Scholar 

  • White RF, Diamond R, Proctor S, Morey C, Hu H (1993) Residual cognitive deficits 50 years after lead poisoning during childhood. Br J Ind Med 50:613–622

    PubMed  CAS  Google Scholar 

  • Wilson MA, Johnston MV, Goldstein GW, Blue ME (2000) Neonatal lead exposure impairs development of rodent barrel field cortex. Proc Natl Acad Sci USA 97:5540–5545

    PubMed  CAS  Google Scholar 

  • Yokel RA (2002) Brain uptake, retention, and efflux of aluminum and manganese. Environ Health Perspect 110(Suppl 5):699–704

    PubMed  CAS  Google Scholar 

  • Yokel RA, Hicks CL, Florence RL (2008) Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese. Food Chem Toxicol 46:2261–2266

    PubMed  CAS  Google Scholar 

  • Yokel RA, Rhineheimer SS, Sharma P, Elmore D, McNamara PJ (2001) Entry, half-life, and desferrioxamine-accelerated clearance of brain aluminum after a single (26)Al exposure. Toxicol Sci 64:77–82

    PubMed  CAS  Google Scholar 

  • Yokel RA, Wilson M, Harris WR, Halestrap AP (2002) Aluminum citrate uptake by immortalized brain endothelial cells: implications for its blood–brain barrier transport. Brain Res 930:101–110

    PubMed  CAS  Google Scholar 

  • Youdim MB (1988) Iron in the brain: implications for Parkinson’s and Alzheimer’s diseases. Mt Sinai J Med 55:97–101

    PubMed  CAS  Google Scholar 

  • Zatta P, Favarato M, Nicolini M (1993) Deposition of aluminum in brain tissues of rats exposed to inhalation of aluminum acetylacetonate. Neuroreport 4:1119–1122

    PubMed  CAS  Google Scholar 

  • Zatta P, Nicosia V, Zambenedetti P (1998) Evaluation of MAO activities on murine neuroblastoma cells upon acute or chronic treatment with aluminium (III) or tacrine. Neurochem Int 32:273–279

    PubMed  CAS  Google Scholar 

  • Zatta P, Zambenedetti P, Milanese M (1999) Activation of monoamine oxidase type-B by aluminum in rat brain homogenate. Neuroreport 10:3645–3648

    PubMed  CAS  Google Scholar 

  • Zhang Z, Buffle J, van Leeuwen HP (2007) Roles of dynamic metal speciation and membrane permeability in metal flux through lipophilic membranes: general theory and experimental validation with nonlabile complexes. Langmuir 23:5216–5226

    PubMed  CAS  Google Scholar 

  • Zhang Z, Buffle J, van Leeuwen HP, Wojciechowski K (2006) Roles of metal ion complexation and membrane permeability in the metal flux through lipophilic membranes. Labile complexes at permeation liquid membranes. Anal Chem 78:5693–5703

    PubMed  CAS  Google Scholar 

  • Zheng K, Pan JW, Ye L, Fu Y, Peng HZ, Wan BY, Gu Q, Bian HW, Han N, Wang JH, Kang B, Pan JH, Shao HH, Wang WZ, Zhu MY (2007) Programmed cell death-involved aluminum toxicity in yeast alleviated by antiapoptotic members with decreased calcium signals. Plant Physiol 143:38–49

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work has been supported by grants from the University of Buenos Aires, Fundación Antorchas, and CONICET, Argentina, and by grants from the National Institute of Environmental Health Services Center for Environmental Health Sciences, University of California, Davis, and from the University of California, Davis. P.I.O. is a member (Investigador correspondiente) of CONICET, Argentina. S.V.V. is a career investigator of CONICET, Argentina.

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  1. Department of Biological Chemistry, IIMHNO (UBA) and IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Sandra V. Verstraeten

  2. Departments of Nutrition and Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Lucila Aimo & Patricia I. Oteiza

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  1. Sandra V. Verstraeten
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  2. Lucila Aimo
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  3. Patricia I. Oteiza
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Correspondence to Patricia I. Oteiza.

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Verstraeten, S.V., Aimo, L. & Oteiza, P.I. Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol 82, 789–802 (2008). https://doi.org/10.1007/s00204-008-0345-3

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