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Mechanistic Effect of Heavy Metals in Neurological Disorder and Brain Cancer

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Networking of Mutagens in Environmental Toxicology

Part of the book series: Environmental Science and Engineering ((ENVSCIENCE))

Abstract

Industrialization era is considered as a part of important human development. Industrialization increases the extensive use of different metals from earth crust because of their materials demand. Extensive use of these materials in daily life and their improper disposal are the reasons for environmental pollution. Toxic metals are highly causative in an open environment and because of this human gets exposures frequently. These toxic metal like cadmium (Cd), lead (Pb), Arsenic (As), Mercury (Hg), Thallium (Th) cross the blood brain barrier to enter into the brain and leads to development of neurodegenerative diseases. Heavy metals play an important role by inducing the reactive oxygen species, mitochondrial dysfunction, calcium ion efflux, an activation of immunogenic response, and suppression of anti-oxidants like catalase, superoxide dismutase (SOD), glutathione. Moreover, the brain-derived neurotrophic factor (BDNF) causes the depletion in cognitive dysfunctions and impairs the memory functions with several other neurological diseases like Alzheimer’s and Parkinson’s diseases. Here we have tried to illustrate the metals evoked mechanism, which impaires the function of neurons and generate the neurotoxicity and neurodegenerative diseases.

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References

  • Agnihotri SK, Agrawal U, Ghosh I (2015) Brain most susceptible to cadmium induced oxidative stress in mice. J Trace Elem Med Biol 30:184–193

    Article  CAS  Google Scholar 

  • Ahlskog JE, Waring SC, Kurland LT, Petersen RC, Moyer TP, Harmsen WS, Bush V (1995) Guamanian neurodegenerative disease: investigation of the calcium metabolism/heavy metal hypothesis. Neurology 45(7):1340–1344

    Article  CAS  Google Scholar 

  • Alizadeh-Ghodsi M, Zavvari A, Ebrahimi-Kalan A, Shiri-Shahsavar MR, Yousefi B (2018) The hypothetical roles of arsenic in multiple sclerosis by induction of inflammation and aggregation of tau protein: a commentary. Nutr Neurosci 21(2):92–96

    Article  Google Scholar 

  • Andrade VM, Aschner M, Marreilha Dos Santos AP (2017) Neurotoxicity of Metal Mixtures. Adv Neurobiol 18:227–265

    Article  CAS  Google Scholar 

  • Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL (2010) Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29(3):730–741

    Article  CAS  Google Scholar 

  • Arini A, Gourves PY, Gonzalez P, Baudrimont M (2015) Metal detoxification and gene expression regulation after a Cd and Zn contamination: an experimental study on Danio rerio. Chemosphere 128:125–133

    Article  CAS  Google Scholar 

  • Arslan M, Demir H, Arslan H, Gokalp AS, Demir C (2011) Trace elements, heavy metals and other biochemical parameters in malignant glioma patients. Asian Pac J Cancer Prev 12(2):447–451

    Google Scholar 

  • Aschner M (2007) Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol 221:131–147

    Article  CAS  Google Scholar 

  • Aschner M, Clarkson TW (1989) Methyl mercury uptake across bovine brain capillary endothelial cells in vitro: the role of amino acids. Pharmacol Toxicol 64:293–297

    Article  CAS  Google Scholar 

  • Ashok A, Rai NK, Tripathi S, Bandyopadhyay S (2015) Exposure to As-, Cd-, and Pb-mixture induces Abeta, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol Sci 143(1):64–80

    Article  CAS  Google Scholar 

  • Ashok BS, Ajith TA, Sivanesan S (2017) Hypoxia-inducible factors as neuroprotective agent in Alzheimer’s disease. Clin Exp Pharmacol Physiol 44(3):327–334

    Article  CAS  Google Scholar 

  • Baker EL, Feldman RG, White RF (1983) The role of occupational lead exposure in the genesis of psychiatric and behavioral disturbances. Acta Psychiatr Scand Suppl 303:38–48

    Article  CAS  Google Scholar 

  • Baranowska-Bosiacka I, Gutowska I, Rybicka M, Nowacki P, Chlubek D (2012) Neurotoxicity of lead hypothetical molecular mechanisms of synaptic function disorders. Neurol Neurochir Pol 46(6):569–578

    Article  CAS  Google Scholar 

  • Bélanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738

    Article  CAS  Google Scholar 

  • Bishak YK, Payahoo L, Osatdrahimi A (2015) Mechanisms of cadmium carcinogenicity in the gastrointestinal tract. Asian Pac J Cancer Prev 16(1):9–21

    Article  Google Scholar 

  • Bostanci MÖ, Bagirici F (2013) Blocking of L-type calcium channels protects hippocampal and nigral neurons against iron neurotoxicity. The role of L-type calcium channels in iron-induced neurotoxicity. Int J Neurosci 123(12):876–882

    Article  CAS  Google Scholar 

  • Caffo M, Caruso G, Fata GL, Barresi V, Visalli M, Venza M, Venza I (2014) Heavy metals and epigenetic alterations in brain tumors. Curr Genomics 15(6):457–463

    Article  CAS  Google Scholar 

  • Caito S, Aschner M (2015) Neurotoxicity of metals. Handb Clin Neurol 131:169–189

    Article  Google Scholar 

  • Camandola S, Mattson MP (2017) Brain metabolism in health, aging, and neurodegeneration. EMBO J 36(11):1474–1492

    Article  CAS  Google Scholar 

  • Carocci A, Rovito N, Sinicropi MS, Genchi G (2014) Mercury toxicity and neurodegenerative effects. Rev Environ Contam Toxicol 229:1–18

    CAS  Google Scholar 

  • Carpenter RL, Jiang BH (2013) Roles of EGFR, PI3 K, AKT, and mTOR in heavy metal-induced cancer. Curr Cancer Drug Targets 13(3):252–266

    Article  CAS  Google Scholar 

  • Caserta D, Graziano A, Monte G, Lo Bordi G, Moscarini M (2013) Heavy metals and placental fetal maternal barrier: a mini review on the major concerns. Eur Rev Med Pharmacol Sci 17(16):2198–2206

    CAS  Google Scholar 

  • Chang SH, Lee HJ, Kang B (2013) Methylmercury induces caspase-dependent apoptosis and autophagy in human neural stem cells. J Toxicol Sci 38(6):823–831

    Article  CAS  Google Scholar 

  • Cherry JD, Olschowka JA, O’Banion MK (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflam 11:15

    Article  CAS  Google Scholar 

  • Chow ES, Hui MN, Lin CC, Cheng SH (2008) Cadmium inhibits neurogenesis in zebrafish embryonic brain development. Aquat Toxicol 87(3):157–169

    Article  CAS  Google Scholar 

  • Chowanadisai W, Kelleher SL, Lonnerdal B (2005) Zinc deficiency is associated with increased brain zinc import and LIV-1 expression and decreased ZnT-1 expression in neonatal rats. J Nutr 135:1002–1007

    Article  CAS  Google Scholar 

  • Christie KJ, Emery B, Denham M, Bujalka H, Cate HS, Turnley AM (2013) Transcriptional regulation and specification of neural stem cells. Adv Exp Med Biol 786:129–155

    Article  CAS  Google Scholar 

  • Clauberg M, Joshi JG (1993) Regulation of serine protease activity by aluminum: implications for Alzheimer disease. Proc Natl Acad Sci USA 90:1009–1012

    Article  CAS  Google Scholar 

  • Cocco P, Dosemeci M, Heineman EF (1998) Brain cancer and occupational exposure to lead. J Occup Environ Med 40(11):937–942

    Article  CAS  Google Scholar 

  • Cocco P, Heineman EF, Dosemeci M (1999) Occupational risk factors for cancer of the central nervous system (CNS) among US women. Am J Ind Med 36(1):70–74

    Article  CAS  Google Scholar 

  • Cui X, Wakai T, Shirai Y, Hatakeyama K, Hirano S (2006) Chronic oral exposure to inorganic arsenate interferes with methylation status of p16INK4a and RASSF1A and induces lung cancer in A/J mice. Toxicol Sci 91(2):372–381

    Article  CAS  Google Scholar 

  • Cvjetko P, Cvjetko I, Pavlica M (2010) Thallium toxicity in humans. Arh Hig Rada Toksikol 61(1):111–119

    Article  CAS  Google Scholar 

  • Davis LE, Kornfeld M, Mooney HS (1994) Methylmercury poisoning: long-term clinical, radiological, toxicological, and pathological studies of an affected family. Ann Neurol 35(6):680–688

    Article  CAS  Google Scholar 

  • Davson H, Welch K, Segal MB (1987) The Secretion of the Cerebrospinal Fluid. The physiology and pathophysiology of the cerebrospinal fluid. Churchill Livingstone, New York, pp 218–221

    Google Scholar 

  • Desai V, Kaler SG (2008) Role of copper in human neurological disorders. Am J Clin Nutr 88(3):855S–858S

    Article  CAS  Google Scholar 

  • Diaz RS, Monreal J (1994) Thallium mediates a rapid chloride/hydroxyl ion exchange through myelin lipid bilayers. Mol Pharmacol 46(6):1210–1216

    CAS  Google Scholar 

  • Doorn JM, Kruer MC (2013) Newly characterized forms of neurodegeneration with brain iron accumulation. Curr Neurol Neurosci Rep 13(12):413

    Article  CAS  Google Scholar 

  • Dorman DC, Brenneman KA, McElveen AM, Lynch SE, Roberts KC, Wong BA (2002) Olfactory transport: a direct route of delivery of inhaled manganese phosphate to the rat brain. J Toxicol Environ Health A 65:1493–1511

    Article  CAS  Google Scholar 

  • Dusek P, Litwin T, Czlonkowska A (2015) Wilson disease and other neurodegenerations with metal accumulations. Neurol Clin 33(1):175–204

    Article  Google Scholar 

  • Evans J, Hastings L (1992) Accumulation of Cd(II) in the CNS depending on the route of administration: intraperitoneal, intratracheal, or intranasal. Fundam Appl Toxicol 19(2):275–278

    Article  CAS  Google Scholar 

  • Farina M, Avila DS, Da Rocha JB (2013) Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int 62(5):575–594

    Article  CAS  Google Scholar 

  • Fondell E, O’Reilly EJ, Fitzgerald KC, Falcone GJ, McCullough ML, Park Y, Kolonel LN, Ascherio A (2013) Magnesium intake and risk of amyotrophic lateral sclerosis: results from five large cohort studies. Amyotroph Lateral Scler Frontotemporal Degener 14(5–6):356–361

    Article  CAS  Google Scholar 

  • Galván-Arzate S, Santamaría A (1998) Thallium toxicity. Toxicol Lett 99(1):1–13

    Article  Google Scholar 

  • Gassowska M, Baranowska-Bosiacka I, Moczydlowska J, Frontczak-Baniewicz M, Gewartowska M, Struzynska L, Adamczyk A (2016) Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring. Toxicology 373:13–29

    Article  CAS  Google Scholar 

  • Giacoppo S, Galuppo M, Calabrò RS, D’Aleo G, Marra A, Sessa E, Bua DG, Potortì AG, Dugo G, Bramanti P, Mazzon E (2014) Heavy metals and neurodegenerative diseases: an observational study. Biol Trace Elem Res 161(2):151–160

    Article  CAS  Google Scholar 

  • Giasson BI, Sampathu DM, Wilson CA, Vogelsberg-Ragaglia V, Mushynski WE, Lee VMY (2002) The environmental toxin arsenite induces tau hyperphosphorylation. Biochemistry 41(51):15376–15387

    Article  CAS  Google Scholar 

  • Gibon J, Tu P, Frazzini V, Sensi SL, Bouron A (2010) The thiol-modifying agent N-ethylmaleimide elevates the cytosolic concentration of free Zn(2 +) but not of Ca(2+) in murine cortical neurons. Cell Calcium 48(1):37–43

    Article  CAS  Google Scholar 

  • Giralt M, Molinero A, Carrasco J, Hidalgo J (2000) Effect of dietary zinc deficiency on brain metallothionein-I and -III mRNA levels during stress and inflammation. Neurochem Int 36(6):555–562

    Article  CAS  Google Scholar 

  • Gorojod RM, Alaimo A, Porte Alcon S (2015) The autophagic-lysosomal pathway determines the fate of glial cells under manganese- induced oxidative stress conditions. Free Radic Biol Med 87:237–251

    Article  CAS  Google Scholar 

  • Gottofrey J, Tjalve H (1991) Axonal transport of cadmium in the olfactory nerve of the pike. Pharmacol Toxicol 69(4):242–252

    Article  CAS  Google Scholar 

  • Graves AB, Rosner D, Echeverria D, Mortimer JA, Larson EB (1998) Occupational exposures to solvents and aluminium and estimated risk of Alzheimer’s disease. Occup Environ Med 55:627–633

    Article  CAS  Google Scholar 

  • Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer’s disease. Neurochem Int 62(5):540–555

    Article  CAS  Google Scholar 

  • Greter M, Merad M (2013) Regulation of microglia development and homeostasis. Glia 61:121–127

    Article  Google Scholar 

  • Grubman A, Pollari E, Duncan C, Caragounis A, Blom T, Volitakis I, Kanninen KM (2014) Deregulation of biometal homeostasis: the missing link for neuronal ceroid lipofuscinoses? Metallomics 6(4):932–943

    Article  CAS  Google Scholar 

  • Gugnani KS, Vu N, Rondon-Ortiz AN, Bohlke M, Maher TJ, Pino-Figueroa AJ (2018) Neuroprotective activity of macamides on manganese-induced mitochondrial disruption in U-87 MG glioblastoma cells. Toxicol Appl Pharmacol 340:67–76

    Article  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 Pb2+. Mol Brain Res 76(2):299–305

    Article  CAS  Google Scholar 

  • Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press

    Google Scholar 

  • Han J, Yang X, Chen X, Li Z, Fang M, Bai B, Tan D (2017) Hydrogen sulfide may attenuate methylmercury-induced neurotoxicity via mitochondrial preservation. Chem Biol Interact 263:66–73

    Article  CAS  Google Scholar 

  • Harris WR (1983) Thermodynamic binding constants of the zinchuman serum transferrin complex. Biochemistry 22:3920–3926

    Article  CAS  Google Scholar 

  • Hart MP, Gitler AD (2012) ALS-associated ataxin 2 polyQ expansions enhance stress-induced caspase 3 activation and increase TDP-43 pathological modifications. J Neurosci 32(27):9133–9142

    Article  CAS  Google Scholar 

  • Heppner FL, Ransohoff RM, Becher B (2015) Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 16:358–372

    Article  CAS  Google Scholar 

  • Hosovski E, Mastelica Z, Sunderic D, Radulovic D (1990) Mental abilities of workers exposed to aluminium. Med Lav 81:119–123

    CAS  Google Scholar 

  • Hossain S, Liu HN, Nguyen M, Shore G, Almazan G (2009) Cadmium exposure induces mitochondria-dependent apoptosis in oligodendrocytes. Neurotoxicology 30(4):544–554

    Article  CAS  Google Scholar 

  • Hussien HM, Abd-Elmegied A, Ghareeb DA, Hafez HS, Ahmed HEA, El-Moneam NA (2018) Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem Toxicol 111:432–444

    Article  CAS  Google Scholar 

  • Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG (2006) Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 26:865–877

    Article  CAS  Google Scholar 

  • Jarup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182

    Article  Google Scholar 

  • Jett DA, Kuhlmann AC, Farmer SJ, Guilarte TR (1997) Age dependent effects of developmental lead exposure on performance in the morris water maze. Pharmacol Biochem Behav 57(1–2):271–279

    Article  CAS  Google Scholar 

  • Jiang LF, Yao TM, Zhu ZL (2007) Impacts of Cd(II) on the conformation and self-aggregation of Alzheimer’s tau fragment corresponding to the third repeat of microtubule-binding domain. Biochim Biophys Acta 1774(11):1414–1421

    Article  CAS  Google Scholar 

  • Joana S, Cristóvão RS, Cláudio MG (2016) Metals and neuronal metal binding proteins implicated in Alzheimer’s Disease. Oxid Med Cell Long 17–47

    Google Scholar 

  • Johansson C, Castoldi AF, Onishchenko N, Manzo L, Vahter M, Ceccatelli S (2007) Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res 11(3–4):241–260

    Article  CAS  Google Scholar 

  • Jung YS, Jeong EM, Park EK, Kim YM, Sohn S, Lee SH, Moon CH (2008) Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells. Eur J Pharmacol 578(1):11–18

    Article  CAS  Google Scholar 

  • Kawahara M, Muramoto K, Kobayashi K, Mori H, Kuroda Y (1994) Aluminum promotes the aggregation of Alzheimer’s amyloid beta-protein in vitro. Biochim Biophys Res Commun 198:531–535

    Article  CAS  Google Scholar 

  • Killin LO, Starr JM, Shiue IJ, Russ TC (2016) Environmental risk factors for dementia: a systematic review. BMC Geriatr 16(1):175

    Article  Google Scholar 

  • Kim MJ, Dunah AW, Wang YT, Sheng M (2005) Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron 46(5):745–760

    Article  CAS  Google Scholar 

  • Kinoshita PF, Yshii LM, Vasconcelos AR, Orellana AM, Lima Lde S, Davel AP, Scavone C (2014) Signaling function of Na, K-ATPase induced by ouabain against LPS as an inflammation model in hippocampus. J Neuroinflam 11:218

    Article  CAS  Google Scholar 

  • Koppenal C, Finefrock AE, Bush AI, Doraiswamy PM (2004) Copper, iron and zinc as therapeutic targets in Alzheimer’s disease. Res Prac Alzheimer’s Dis 9:250–255

    CAS  Google Scholar 

  • Kumar P, Sannadi S, Reddy R (2013) Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: reversal effect of essential metals and a chelating agent 6(3):1150–1166

    Google Scholar 

  • Kumudini N, Uma A, Devi YP, Naushad SM, Mridula R, Borgohain R, Kutala VK (2014) Association of Parkinson’s disease with altered serum levels of lead and transition metals among South Indian subjects. Indian J Biochem Biophys 51(2):121–126

    CAS  Google Scholar 

  • Lafon Cazal M, Pietri S, Culcasi M, Bockaert J (1993) NMDA dependent superoxide production and neurotoxicity. Nature 364(3):535–537

    Article  CAS  Google Scholar 

  • Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN (2015) Cancer stem cells in glioblastoma. Genes Dev 29(12):1203–1217

    Article  CAS  Google Scholar 

  • LeBel CP, Ali SF, McKee M, Bondy SC (1990) Organometal induced increases in oxygen reactive species: the potential of 2′,7′-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol Appl Pharmacol 104(1):17–24

    Article  CAS  Google Scholar 

  • Lemercier V, Millot X, Ansoborlo E, Menetrier F, Flury-Herard A, Rousselle C, Scherrmann JM (2003) Study of uranium transfer across the blood-brain barrier. Radiat Prot Dosimetry 105(1–4):243–245

    Article  CAS  Google Scholar 

  • Li W, Garringer HJ, Goodwin CB, Richine B, Acton A, VanDuyn N, Vidal R (2015) Systemic and cerebral iron homeostasis in ferritin knock-out mice. PLoS One 10(1):e0117435

    Article  CAS  Google Scholar 

  • Liu Y, Wu H, Kou L, Liu X, Zhang J, Guo Y, Ma E, (2014) Two metallothionein genes in Oxya chinensis: molecular characteristics, expression patterns and roles in heavy metal stress. PLoS One 12:9(11)

    Article  CAS  Google Scholar 

  • Loef M, Walach H (2015) Iron and copper in alzheimer’s disease: a review micronutrients in dementia and cognitive decline, pp 563–571

    Google Scholar 

  • Lohren H, Blagojevic L, Fitkau R, Ebert F, Schildknecht S, Leist M, Schwerdtle T (2015) Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes. J Trace Elem Med Biol 32:200–208

    Article  CAS  Google Scholar 

  • Lopez GC, Varea E, Palop JJ, Nacher J, Ramirez C, Ponsoda X, Molowny A (2002) Cytochemical techniques for zinc and heavy metals localization in nerve cells. Microsc Res Tech 56(5):318–331

    Article  Google Scholar 

  • Lynam DR, Roos JW, Pfeifer GD, Fort BF, Pullin TG (1999) Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline. Neurotoxicol 20:145–150

    Google Scholar 

  • Mantyh PW, Ghilardi JR, Rogers S, DeMaster E, Allen CJ, Stimson ER, Maggio JE (1993) Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem 61:1171–1174

    Article  CAS  Google Scholar 

  • Martinez EJ, Kolb BL, Bell A, Savage DD, Allan AM (2008) Moderate perinatal arsenic exposure alters neuroendocrine markers associated with depression and increases depressive-like behaviors in adult mouse offspring. Neurotoxicology 29(4):647–655

    Article  CAS  Google Scholar 

  • Martinez-Finley EJ, Gavin CE, Aschner M (2013) Manganese neurotoxicity and the role of reactive oxygen species. Free Radic Biol Med 62:65–75

    Article  CAS  Google Scholar 

  • Mason LH, Harp JP, Han DY (2014) Pb neurotoxicity: neuropsychological effects of lead toxicity. Biomed Res Int 2014:840547

    Google Scholar 

  • McCarthy RC, Sosa JC, Gardeck AM, Baez AS, Lee CH, Resnick MW (2018) Inflammation-induced iron transport and metabolism by brain microglia. J Biol Chem RA118.001949. https://doi.org/10.1074/jbc.ra118.001949

    Article  CAS  Google Scholar 

  • Mergenthaler P, Lindauer U, Dienel GA, Meisel A (2013) Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 36(10):587–597

    Article  CAS  Google Scholar 

  • Meyer E, Kurian MA, Hayflick SJ (2015) Neurodegeneration with brain iron accumulation: genetic diversity and pathophysiological mechanisms. Annu Rev Genomics Hum Genet 16:257–279

    Article  CAS  Google Scholar 

  • Modabbernia A, Velthorst E, Gennings C, De Haan L, Austin C, Sutterland A, Reichenberg A (2016) Early-life metal exposure and schizophrenia: a proof-of-concept study using novel tooth-matrix biomarkers. Eur Psychiatry 36:1–6

    Article  CAS  Google Scholar 

  • Mohamed Fel B, Zaky EA, El-Sayed AB, Elhossieny RM, Zahra SS, Salah Eldin W, Youssef WY, Khaled RA, Youssef AM (2015) Assessment of hair aluminum, lead, and mercury in a sample of autistic Egyptian children: environmental risk factors of heavy metals in Autism. Behav Neurol 2015:545674

    Google Scholar 

  • Mohandas B, Colvin RA (2004) The role of zinc in Alzheimer’s disease. Recent Res Devel Physiol 2:225–245

    CAS  Google Scholar 

  • Moretto MB, Funchal C, Santos AQ, Gottfried C, Boff B, Zeni G, Rocha JB (2005) Ebselen protects glutamate uptake inhibition caused by methyl mercury but does not by Hg2+. Toxicology 214(1–2):57–66

    Article  CAS  Google Scholar 

  • Murakami M, Hirano T (2008) Intracellular zinc homeostasis and zinc signaling. Cancer Sci 99(8):1515–1522

    Article  CAS  Google Scholar 

  • Nathanson D, Mischel PS (2011) Charting the course across the blood-brain barrier. J Clin Invest 121(1):31–33

    Article  CAS  Google Scholar 

  • Neal AP, Worley PF, Guilarte TR (2011) Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA receptor inhibition. Neurotoxicology 32(2):281–289

    Article  CAS  Google Scholar 

  • Nelson N (1999) Metal ion transporters and homeostasis. EMBO J 18:4361–4371

    Article  CAS  Google Scholar 

  • Nori A, Fulceri R, Gamberucci A, Benedetti A, Volpe P (1996) Biochemical and functional heterogeneity of rat cerebrum microsomal membranes in relation to SERCA Ca(2 +)-ATPases and Ca2 + release channels. Cell Calcium 19(5):375–381

    Article  CAS  Google Scholar 

  • Notarachille G, Arnesano F, Calo V, Meleleo D (2014) Heavy metals toxicity: effect of cadmium ions on amyloid beta protein 1-42. Possible implications for Alzheimer’s disease. Biometals 27(2):371–388

    CAS  Google Scholar 

  • Okuda B, Iwamoto Y, Tachibana H (1997) Parkinsonism after acute cadmium poisoning. Clin Neurol Neurosurg 99(4):263–265

    Article  CAS  Google Scholar 

  • Oliver KR, Fazakerley JK (1998) Transneuronal spread of Semliki Forest virus in the developing mouse olfactory system is determined by neuronal maturity. Neurosci 82:867–877

    Article  CAS  Google Scholar 

  • Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA. 310(17):1842–1850

    Article  CAS  Google Scholar 

  • Orrenius S, Nicotera P (1994a) The calcium ion and cell death. J Neural Transm Suppl 43:1–11

    CAS  Google Scholar 

  • Orrenius S, Nicotera P (1994b) The calcium ion and cell death. J Neural Transm Suppl 43:1–11

    CAS  Google Scholar 

  • Osorio-Rico L, Santamaria A, Galvan-Arzate S (2017) Thallium toxicity: general issues, neurological symptoms, and neurotoxic mechanisms. Adv Neurobiol 18:345–353

    Article  Google Scholar 

  • Pal R, Nath R, Gill KD (1993) Influence of ethanol on cadmium accumulation and its impact on lipid peroxidation and membrane bound functional enzymes (Na + , K + -ATPase and acetylcholinesterase) in various regions of adult rat brain. Neurochem Int 23(5):451–458

    Article  CAS  Google Scholar 

  • Pamphlett R, Kum Jew S (2016) Locus ceruleus neurons in people with autism contain no histochemically-detectable mercury. Biometals 29(1):171–175

    Article  CAS  Google Scholar 

  • Parkinson DK, Ryan C, Bromet EJ (1986) A psychiatric epidemiologic study of occupational lead exposure. Am J Epidemiol 123(2):261–269

    Article  CAS  Google Scholar 

  • Parks JM, Johs A, Podar M (2013) The genetic basis for bacterial mercury methylation. Science 339(6125):1332–1335

    Article  CAS  Google Scholar 

  • Pelclová D, Urban P, Ridzon P (2009) Two-year follow-up of two patients after severe thallium intoxication. Hum Exp Toxicol 28(5):263–272

    Article  Google Scholar 

  • Pentyala S, Ruggeri J, Veerraju A, Yu Z, Bhatia A, Desaiah D, Vig P (2010) Microsomal Ca2 + flux modulation as an indicator of heavy metal toxicity. Indian J Exp Biol 48(7):737–743

    CAS  Google Scholar 

  • Peres TV, Schettinger MR, Chen P, Carvalho F, Avila DS, Bowman AB, Aschner M (2016) Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies. BMC Pharmacol Toxicol 17(1):57

    Article  CAS  Google Scholar 

  • Perl DP (2001) The association of aluminum and neurofibrillary degeneration in Alzheimer’s disease, a personal perspective. In Exley C (ed) Aluminum and Alzheimer’s disease. Elsevier, pp 133–146

    Google Scholar 

  • Prakash C, Soni M, Kumar V (2016) Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review. J Appl Toxicol 36(2):179–188

    Article  CAS  Google Scholar 

  • Quadri M, Federico A, Zhao T (2012) Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. Am J Hum Genet 90(3):467–477

    Article  CAS  Google Scholar 

  • Rai A, Maurya SK, Khare P, Srivastava A, Bandyopadhyay S (2010) Characterization of developmental neurotoxicity of As, Cd, and Pb mixture: synergistic action of metal mixture in glial and neuronal functions. Toxicol Sci 118(2):586–601

    Article  CAS  Google Scholar 

  • Rao DB, Wong BA, McManus BE, McElveen AM, James AR, Dorman DC (2003) Inhaled iron, unlike manganese, is not transported to the rat brain via the olfactory pathway. Toxicol Appl Pharmacol 193:116–126

    Article  CAS  Google Scholar 

  • Reinholz MM, Bertics PJ, Miletic V (1999) Chronic exposure to lead acetate affects the development of protein kinase C activity and the distribution of the PKCgamma isozyme in the rat hippocampus. Neurotoxicology 20(4):609–617

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Ríos C, Galván-Arzate S, Tapia R (1989) Brain regional thallium distribution in rats acutely intoxicated with Tl2SO4. Arch Toxicol 63(1):34–37

    Article  Google Scholar 

  • Robison G, Sullivan B, Cannon JR (2015) Identifcation of dopaminergic neurons of the substantia nigra pars compacta as a target of manganese accumulation. Metallomics 7(5):748–755

    Article  CAS  Google Scholar 

  • Roos PM, Vesterberg O, Nordberg M (2006) Metals in motor neuron diseases. Exp Biol Med (Maywood) 231(9):1481–1487

    Article  CAS  Google Scholar 

  • Rudgalvyte M, Peltonen J, Lakso M (2016) RNA-seq reveals acute manganese exposure increases endoplasmic reticulum related and lipocalin mRNAs in caenorhabditis elegans. J Biochem Mol Toxicol 30(2):97–105

    Article  CAS  Google Scholar 

  • Saha A (2005) Thallium toxicity: a growing concern. Indian J Occup Environ Med 9(2):53–56

    Article  Google Scholar 

  • Salvador GA, Uranga RM, Giusto NM (2010) Iron and mechanisms of neurotoxicity. Int J Alzheimers Dis 2011:720658

    Google Scholar 

  • Serlin Y, Shelef I, Knyazer B, Friedman A (2015) Anatomy and physiology of the blood-brain barrier. Semin Cell Dev Biol 38:2–6

    Article  Google Scholar 

  • Shaw CA, Tomljenovic L (2013) Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol Res 56(2–3):304–316

    Article  CAS  Google Scholar 

  • Sheehan MC, Burke TA, Navas-Acien A (2014) Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review. Bull World Health Organ 92(4):254–269F

    Article  Google Scholar 

  • Shen XM, Dryhurst G (1998) Iron- and manganese-catalyzed autoxidation of dopamine in the presence of l-cysteine: possible insights into iron- and manganesemediated dopaminergic neurotoxicity. Chem Res Toxicol 11(7):824–837

    Article  CAS  Google Scholar 

  • Simmons-Willis TA, Koh AS, Clarkson TW, Ballatori N (2002) Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem J 367(Pt 1):239–246

    Article  CAS  Google Scholar 

  • Singh D, Banerji AK, Dwarakanath BS, Tripathi RP, Gupta JP, Mathew TL, Jain V (2005) Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol 181(8):507–514

    Article  Google Scholar 

  • Sparks DL, Schreurs BG (2003) Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. Proc Natl Acad Sci USA 100:11065–11069

    Article  CAS  Google Scholar 

  • Stackelberg KV, Elizabeth G, Tian C, Birgit CH (2013) Mixtures, metals, genes and pathways: a systematic review. Working Paper prepared for: methods for research synthesis: a cross-disciplinary workshop. Harvard Center for Risk Analysis, 3 Oct 2013

    Google Scholar 

  • Straka E, Ellinger I, Balthasar C, Scheinast M, Schatz J, Szattler T, Gundacker C (2016) Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters. Toxicology 340:34–42

    Article  CAS  Google Scholar 

  • Sun X, He Y, Guo Y, Li S, Zhao H, Wang Y, Xing M (2017) Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues. BMC Vet Res 13(1):157

    Article  CAS  Google Scholar 

  • Suzuki T, Shishido S, Ishihara N (1976) Different behaviour of inorganic and organic mercury in renal excretion with reference to effects of D-penicillamine. Br J Ind Med 33(2):88–91

    CAS  Google Scholar 

  • Szabo ST, Harry GJ, Hayden KM, Szabo DT, Birnbaum L (2016) Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer’s Disease and Nondemented Elderly Controls. Toxicol Sci 150(2):292–300

    Article  CAS  Google Scholar 

  • Takeda A, Suzuki M, Okada S, Oku N (2000) Zn localization in rat brain after intracerebroventricular injection of 65Zn-histidine. Brain Res 863:241–244

    Article  CAS  Google Scholar 

  • Tuschl K, Clayton PT, Gospe SM Jr (2012) Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet 90(3):457–466

    Article  CAS  Google Scholar 

  • Tykwinska K, Lauster R, Knaus P, Rosowski M (2013) Growth and differentiation factor 3 induces expression of genes related to differentiation in a model of cancer stem cells and protects them from retinoic acid-induced apoptosis. PLoS One 8(8):e70612

    Article  CAS  Google Scholar 

  • Van Wijngaarden E, Dosemeci M (2006) Brain cancer mortality and potential occupational exposure to lead: findings from the national longitudinal mortality study, 1979–1989. Int J Cancer 119:1136–1144

    Article  CAS  Google Scholar 

  • Vu HT, Kobayashi M, Hegazy AM, Tadokoro Y, Ueno M, Kasahara A, Hirao A (2018) Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas. Cancer Sci. (https://doi.org/10.1111/cas.13695 (Epub ahead of print)

    Article  CAS  Google Scholar 

  • Waly M, Power-Charnitsky VA, Hodgson N, Sharma A, Audhya T, Zhang Y, Deth R (2016) Alternatively spliced methionine synthase in SH-SY5Y neuroblastoma cells: cobalamin and GSH dependence and inhibitory effects of neurotoxic metals and thimerosal. Oxid Med Cell Longev 6143753

    Google Scholar 

  • Wang B, Du Y (2013) Cadmium and its neurotoxic effects. Oxid Med Cell Longev 2013:898034

    Google Scholar 

  • Wegst USR, Mullin EJ, Ding D, Manohar S, Salvi R, Aga DS, Roth JA (2015) Endogenous concentrations of biologically relevant metals in rat brain and cochlea determined by inductively coupled plasma mass spectrometry. Biometals 28(1):187–196

    Article  CAS  Google Scholar 

  • Wesseling C, Pukkala E, Neuvonen K, Kauppinen T, Boffetta P, Partanen T (2002) Cancer of the brain and nervous system and occupational exposures in Finnish women. J Occup Environ Med 4(7):663–668

    Article  Google Scholar 

  • White DM, Longstreth WT, JrL Rosenstock, Claypoole KH, Brodkin CA, Townes BD (1992) Neurologic syndrome in 25 workers from an aluminum smelting plant. Arch Intern Med 152:1443–1448

    Article  CAS  Google Scholar 

  • Wu MJ, Hu HH, Siao CZ, Liao YM, Chen JH, Li MY, Chen YF (2018) All Organic Label-like Copper(II) Ions Fluorescent Film Sensors with High Sensitivity and Stretchability. ACS Sens 3(1):99–105

    Article  CAS  Google Scholar 

  • Yang H, Wu J, Guo R, Peng Y, Zheng W, Liu D, Song Z (2013) Glycolysis in energy metabolism during seizures. Neural Regen Res 8(14):1316–1326

    CAS  Google Scholar 

  • Yang T, Xu Z, Liu W, Feng S, Li H, Guo M, Xu B (2017) Alpha-lipoic acid reduces methylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways. Environ Toxicol 32(3):931–943

    Article  CAS  Google Scholar 

  • Yassa HA (2014) Autism: a form of lead and mercury toxicity. Environ Toxicol Pharmacol 38(3):1016–1024

    Article  CAS  Google Scholar 

  • Yin JC, Wallach JS, Del Vecchio M, Wilder EL, Zhou H, Quinn WG, Tully T (1994) Induction of a dominant negative CREB transgene specifically blocks long term memory in drosophila. Cell 79(1):49–58

    Article  CAS  Google Scholar 

  • Yokel RA (2006) Blood brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal induced neurodegeneration. J Alzheimers Dis 10(2–3):223–253

    Article  Google Scholar 

  • Yokel RA, Florence RL (2006) Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water. Toxicology 227(1–2):86–93

    Article  CAS  Google Scholar 

  • Yuntao F, Chenjia G, Panpan Z (2016) Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes. Arch Toxicol 90(2):333–345

    Article  CAS  Google Scholar 

  • Zeineh MM, Chen Y, Kitzler HH, Hammond R, Vogel H, Rutt BK (2015) Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease. Neurobiol Aging 36:2483–2500

    Article  CAS  Google Scholar 

  • Zevin S, Benowitz NL (1999) Drug interactions with tobacco smoking. An update. Clin Pharmacokinet 36(6):425–438

    Article  CAS  Google Scholar 

  • Zhang Z, Miah M, Culbreth M, Aschner M (2016) Autophagy in neurodegenerative diseases and metal neurotoxicity. Neurochem Res 41(1–2):409–422

    Article  CAS  Google Scholar 

  • Zhang C, Jiang H, Wang P, Liu H, Sun X (2017) Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions. Sci Rep 7:44708

    Article  CAS  Google Scholar 

  • Zhao G, Ding M, Zhang B (2008) Clinical manifestations and management of acute thallium poisoning. Eur Neurol 60(6):292–297

    Article  CAS  Google Scholar 

  • Zheng W, Aschner M, Ghersi-Egea JF (2003) Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicol Appl Pharmacol 192(1):1–11

    Article  CAS  Google Scholar 

  • Zucca FA, Segura-Aguilar J, Ferrari E, Muñoz P, Paris I, Sulzer D, Sarna T, Casella L, Zecca L (2017) Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog Neurobiol 155:96–119

    Article  CAS  Google Scholar 

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Agnihotri, S.K., Kesari, K.K. (2019). Mechanistic Effect of Heavy Metals in Neurological Disorder and Brain Cancer. In: Kesari, K. (eds) Networking of Mutagens in Environmental Toxicology. Environmental Science and Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-96511-6_2

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