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Neurotoxicity Research

, Volume 11, Issue 3–4, pp 241–260 | Cite as

Neurobehavioural and molecular changes induced by methylmercury exposure during development

  • Carolina JohanssonEmail author
  • Anna F. Castoldi
  • Natalia Onishchenko
  • Luigi Manzo
  • Marie Vahter
  • Sandra Ceccatelli
Article

Abstract

There is an increasing body of evidence on the possible environmental influence on neurodevelopmental and neurodegenerative disorders. Both experimental and epidemiological studies have demonstrated the distinctive susceptibility of the developing brain to environmental factors such as lead, mercury and polychlorinated biphenyls at levels of exposure that have no detectable effects in adults. Methylmercury (MeHg) has long been known to affect neurodevelopment in both humans and experimental animals. Neurobehavioural effects reported include altered motoric function and memory and learning disabilities. In addition, there is evidence from recent experimental neurodevelopmental studies that MeHg can induce depression-like behaviour. Several mechanisms have been suggested fromin vivo- andin vitro-studies, such as effects on neurotransmitter systems, induction of oxidative stress and disruption of microtubules and intracellular calcium homeostasis. Recentin vitro data show that very low levels of MeHg can inhibit neuronal differentiation of neural stem cells. This review summarises what is currently known about the neurodevelopmental effects of MeHg and consider the strength of different experimental approaches to study the effects of environmentally relevant exposurein vivo andin vitro.

Keywords

Methylmercury Neuro-ontogeny Neurites Development Neurochemistry Neuropathology Neurobehaviour Cell death Oxidative stress Calcium Microtubules 

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References

  1. Ahlborm E, V Gogvadze, M Chen, G Celsi and S Ceccatelli(2000) Prenatal exposure to high levels of glucocorticoidsincreases the susceptibility of cerebellar granule cells tooxidative stress-induced cell death.Proc. Natl. Acad. Sci. 97, 14726–14730.Google Scholar
  2. Aschner M, CP Yao, J Allen and KH Tan (2000) Methylmercuryalters glutamate transport in astrocytes.Neurochem. Int. 37, 199–206.PubMedGoogle Scholar
  3. Atchison WD and MF Hare (1994) Mechanisms of methylmer-cury-inducedneurotoxicity.FASEB J. 8, 622–629.PubMedGoogle Scholar
  4. Baraldi M, P Zanoli P, F Tascedda, JMC Blom and N Brunello(2002) Cognitive deficits and changes in gene expression ofNMDA receptors after prenatal methylmercury exposure.Environ. Health Perspect. 110 (Suppl. 5), 855–858.PubMedGoogle Scholar
  5. Bartolome J, WL Whitmore, FJ Seidler and TA Slotkin (1984)Exposure to methylmercuryin utero: effects on biochemicaldevelopment of catecholamine neurotransmitter systems.Life Sci. 35, 657–670.PubMedGoogle Scholar
  6. Bartolome JV, RJ Kavlock, T Cowdery, L Orband-Miller and TA Slotkin (1987) Development of adrenergic receptor bindingsites in brain regions of the neonatal rat: effects of prenatalor postnatal exposure to methylmercury.Neurotoxicology 8, 1–13.PubMedGoogle Scholar
  7. Belletti S, G Orlandini, MV Vettori, A Mutti, J Uggeri, R Scandroglio, R Alinovi and R Gatti (2002) Time courseassessment of methylmercury effects on C6 glioma cells:submicromolar concentrations induce oxidative DNA damageand apoptosis.J. Neurosci. Res. 70, 703–711.PubMedGoogle Scholar
  8. Berridge MJ, P Lipp and MD Bootman (2000) The versatilityand universality of calcium signalling.Nat. Rev. Mol. CellBiol. 1, 11–21.Google Scholar
  9. Beyrouty P, CJ Stamler, JN Liu, KM Loua, S Kubow and HM Chan (2006) Effects of prenatal methylmercury exposure onbrain monoamine oxidase activity and neurobehaviour ofrats.Neurotoxicol. Teratol. 28, 251–259.PubMedGoogle Scholar
  10. Bland C and MD Rand (2006) Methylmercury induces activationof Notch signaling.Neurotoxicology 27, 982–991.PubMedGoogle Scholar
  11. Bozzi Y and E Borrelli (2006) Dopamine in neurotoxicity andneuroprotection: what do D2 receptors have to do with it?Trends Neurosci. 29, 167–174.PubMedGoogle Scholar
  12. Burbacher TM, KS Grant and NK Mottet (1986) Retardedobject permanence development in methylmercury exposedMacaca fascicularis infants.Dev. Psychobiol. 22, 771–776.Google Scholar
  13. Burbacher TM, PM Rodier and B Weiss (1990a) Methylmercurydevelopmental neurotoxicity: a comparison of effects inhumans and animals.Neurotoxicol. Teratol. 12, 191–202.PubMedGoogle Scholar
  14. Burbacher TM, GP Sackett and NK Mottet (1990b)Methylmercury effects on the social behavior ofMacacafascicularis infants.Neurotoxicol. Teratol. 12, 65–71.PubMedGoogle Scholar
  15. Burbacher TM, KS Grant, DB Mayfield, SG Gilbert and DC Rice (2005) Prenatal methylmercury exposure affects spatialvision in adult monkeys.Toxicol. Appl. Pharmacol. 208, 21–28.PubMedGoogle Scholar
  16. Cagiano R, MA De Salvia, G Renna, E Tortella, D Braghiroli, C Parenti, P Zanoli, M Baraldi, Z Annau and V Cuomo (1990) Evidence that exposure to methylmercury duringgestation induces behavioral and neurochemical changes inoffspring of rats.Neurotoxicol. Teratol. 12, 23–28.PubMedGoogle Scholar
  17. Carratù MR, P Borracci, A Coluccia, A Giustino, G Renna, MC Tomasini, E Raisi, T Antonelli, V Cuomo, E Mazzonib and L Ferraro (2006) Acute exposure to methylmercury attwo developmental windows: focus on neurobehavioral andneurochemical effects in rat offspring.Neuroscience 141, 1619–1629.PubMedGoogle Scholar
  18. Castoldi AF, S Barni, I Turin, C Gandini and L Manzo (2000)Early acute necrosis, delayed apoptosis and cytoskeletalbreakdown in cultured cerebellar granule neurons exposedto methylmercury.J. Neurosci. Res. 59, 775–787.PubMedGoogle Scholar
  19. Castoldi AF, T Coccini, S Ceccatelli and L Manzo (2001)Neurotoxicity and molecular effects of methylmercury.Brain Res. Bull. 55, 197–203.PubMedGoogle Scholar
  20. Castoldi AF, F Blandini, G Randine, A Samuele, L Manzo andT Coccini (2006) Brain monoaminergic neurotransmissionparameters in weanling rats after perinatal exposure tomethylmercury and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153).Brain Res. 1112, 91–98.PubMedGoogle Scholar
  21. Chandra J, A Samali and S Orrenius (2000) Triggering andmodulation of apoptosis by oxidative stress.Free Radic.Biol. Med. 29, 323–333.PubMedGoogle Scholar
  22. Chang LW, KR Reuhl and JM Spyker (1977) Ultrastructuralstudy of the latent effects of methyl mercury on the nervoussystem after prenatal exposure.Environ. Res. 13, 171–185.PubMedGoogle Scholar
  23. Choi BH, LW Lapham, L Amin-Zaki and T Saleem (1978)Abnormal neuronal migration, deranged cerebral corticalorganization, and diffuse white matter astrocytosis of humanfetal brain: a major effect of methylmercury poisoninginutero. J. Neuropathol. Exp. Neurol. 37, 719–733.Google Scholar
  24. Choi BH, M Kudo and LW Lapham (1981) A Golgi andelectron-microscopy study of cerebellum in methylmercury-poisonedneonatal mice.Acta Neurotpathol. (Berl.) 54, 233–237.Google Scholar
  25. Clarkson TW (1972) The pharmacology of mercury compounds.Annu. Rev. Pharmacol. 12, 375–406.PubMedGoogle Scholar
  26. Clarkson TW (2002) The three modern faces of mercury.Environ. Health Perspect. 110 (Suppl. 1), 11–23.PubMedGoogle Scholar
  27. Clarkson TW, LMagos, C Cox, MR Greenwood, L Amin-Zaki, MA Majeed and SF Al-Damluji (1981) Tests of efficacy ofantidotes for removal of methylmercury in human poisoningduring the Iraq outbreak.J. Pharmacol. Exp. Ther. 218, 74–83.PubMedGoogle Scholar
  28. Coccini T, G Randine, SM Candura, R Nappi, LD Prockopand L Manzo (2000) Low-level exposure to methylmercurymodifies muscarinic cholinergic receptor binding characteristicsin rat brain and lymphocytes: physiologic implicationsand new opportunities in biological monitoring.Environ.Health Perspect. 108, 29–33.PubMedGoogle Scholar
  29. Coccini T, G Randine, AF Castoldi, P Grandjean, G Ostendorp, B Heinzow and L Manzo (2006) Effects of developmentalco-exposure to methylmercury and 2,2′,4,4′,5,5′-hexachloro-biphenyl (PCB153) on cholinergic muscarinic receptors inrat brain.Neurotoxicology 27, 468–477.PubMedGoogle Scholar
  30. Daré E, ME Gotz, B Zhivotovsky, L Manzo and S Ceccatelli(2000) Antioxidants J811 and 17beta-estradiol protect cerebellargranule cells from methylmercury-induced apoptoticcell death.J. Neurosci. Res. 62, 557–565.PubMedGoogle Scholar
  31. Daré E, AM Gorman, E Ahlbom, M Götz, T Momoi and S Ceccatelli (2001a) Apoptotic morphology does not alwaysrequire caspase activity in rat cerebellar granule neurons.Neurotox. Res. 3, 501–514.PubMedGoogle Scholar
  32. Daré E, W Li, B Zhivotovsky, X Yuan and S Ceccatelli (2001b)Methylmercury and H2O2 provoke lysosomal damage inhuman astrocytoma D384 cells followed by apoptosis.FreeRadic. Biol. Med. 30, 1347–1356.Google Scholar
  33. Daré E, S Fetissov, T Hökfelt, H Hall, SO Ögren and S Ceccatelli (2003) Effects of prenatal exposure to methylmercuryon dopamine-mediated locomotor activity and dopamineD2 receptor binding.Naunyn Schmiedebergs Arch.Pharmacol. 367, 500–508.PubMedGoogle Scholar
  34. Davidson PW, GJ Myers, C Cox, GE Wilding, CF Shamlaye, LS Huang, E Cernichiari, J Sloane-Reeves, D Palumbo and TW Clarkson (2006) Methylmercury and neurodevelopment:longitudinal analysis of the Seychelles child developmentcohort.Neurotoxicol. Teratol. 28, 529–535.PubMedGoogle Scholar
  35. Debes F, E Budtz-Jorgensen, P Weihe, RF White and P Grandjean (2006) Impact of prenatal methylmercuryexposure on neurobehavioral function at age 14 years.Neurotoxicol. Teratol. 28, 363–375.PubMedGoogle Scholar
  36. Dey PM, M Gochfeld and KR Reuhl (1999) Developmentalmethylmercury administration alters cerebellar PSA-NCAMexpression and Golgi sialyltransferase activity.Brain Res. 845, 139–151.PubMedGoogle Scholar
  37. Dickson BJ (2002) Molecular mechanisms of axon guidance.Science 298, 1959–1964.PubMedGoogle Scholar
  38. Doré FY, S Goulet, A Gallagher, PO Harvey, JF Cantin, TD Aigle, ME Mirault (2001) Neurobehavioral changes in micetreated with methylmercury at two different stages of fetaldevelopment.Neurotoxicol. Teratol. 23, 463–472.PubMedGoogle Scholar
  39. Duchen MR (2000) Mitochondria and Ca(2+)in cell physiologyand pathophysiology.Cell Calcium 28, 339–348.PubMedGoogle Scholar
  40. EPA-US (1990) An assessment of exposure to mercury inthe United States, in:Environmental Protection Agency(US). Mercury study report to Congress, Vol. IV (EPA,Washington).Google Scholar
  41. Farina M, KC Dahm, FD Schwalm, AM Brusque, ME Frizzo, G Zeni, DO Souza and JB Rocha (2003) Methylmercuryincreases glutamate release from brain synaptosomes andglutamate uptake by cortical slices from suckling rat pups:modulatory effect of ebselen.Toxicol. Sci. 73, 135–140.PubMedGoogle Scholar
  42. Faustman EM, RA Ponce, YC Ou, MA Mendoza, T Lewandowski and T Kavanagh (2002) Investigations ofmetylmercury-induced alterations in neurogenesis.Environ.Health Perspect. 110 (Suppl. 5), 859–864.PubMedGoogle Scholar
  43. Ferguson SA (1996) Neuroanatomical and functional alterationsresulting from early postnatal cerebellar insults inrodents.Pharmacol. Biochem. Behav. 55, 663–671.PubMedGoogle Scholar
  44. Fonfria E, E Daré, M Benelli, C Sunol and S Ceccatelli (2002)Translocation of apoptosis-inducing factor in cerebellargranule cells exposed to neurotoxic agents inducing oxidativestress.Eur. J. Neurosci. 16, 2013–2016.PubMedGoogle Scholar
  45. Franco JL, A Teixeira, FC Meotti, CM Ribas, J Stringari, SCG Pomblum, AM Moro, D Bohrer, AV Bairros, AL Dafre, ARS Santos and M Farina (2006) Cerebellar thiol status andmotor deficit after lactational exposure to methylmercury.Environ. Res. 102, 22–28.PubMedGoogle Scholar
  46. Fredriksson A, L Dencker, T Archer and BR Danielsson (1996)Prenatal coexposure to metallic mercury vapour and methylmercuryproduce interactive behavioural changes in adultrats.Neurotoxicol. Teratol. 18, 129–134.PubMedGoogle Scholar
  47. Fujita K, P Lazarovici and G Guroff (1989) Regulation of thedifferentiation of PC12 pheochromocytoma cells.Environ.Health Perspect. 80, 127–142.PubMedGoogle Scholar
  48. Fujiyama J, K Hirayama and A Yasutake (1994) Mechanismof methylmercury efflux from cultured astrocytes.Biochem.Pharmacol. 47, 1525–1530.PubMedGoogle Scholar
  49. Gallo G and PC Letourneau (2004) Regulation of growth coneactin filaments by guidance cues.J. Neurobiol. 58, 92–102.PubMedGoogle Scholar
  50. Garg TK and JY Chang (2006) Methylmercury causes oxidativestress and cytotoxicity in microglia: attenuation by15-deoxy-delta 12, 14-prostaglandin J2.J. Neuroimmunol. 171, 17–28.PubMedGoogle Scholar
  51. Gasso S, RM Cristofol, G Selema, R Rosa, E Rodriguez-Farreand C Sanfeliu (2001) Antioxidant compounds and Ca(2+)pathway blockers differentially protect against methylmercuryand mercuric chloride neurotoxicity.J. Neurosci. Res. 66, 135–145.PubMedGoogle Scholar
  52. Gatti R, S Belletti, J Uggeri, MV Vettori, AMutti, R Scandroglioand G Orlandini (2004) Methylmercury cytotoxicity inPC 12 cells is mediated by primary glutathione depletionindependent of excess reactive oxygen species generation.Toxicology 204, 175–185.PubMedGoogle Scholar
  53. Gilbert SG and KS Grant-Webster (1995) Neurobehavioraleffects of developmental methylmercury exposure.Environ.Health Perspect. 103 (Suppl. 6), 135–142.PubMedGoogle Scholar
  54. Gilbert SG, DC Rice and TM Burbacher (1996) Fixed-interval/fixed ratio performance in adult monkeys exposedin uteroto methylmercury.Neurotoxicol. Teratol. 18, 539–546.PubMedGoogle Scholar
  55. Gimenez-Llort L, E Ahlbom, E Daré, M Vahter, S Ögrenand S Ceccatelli (2001) Prenatal exposure to methylmercurychanges dopamine-modulated motor activity duringearly ontogeny: age and gender-dependent effects.Environ.Toxicol. Pharmacol. 9, 61–70.PubMedGoogle Scholar
  56. Graff RD, MM Falconer, DL Brown and KR Reuhl (1997)Altered sensitivity of posttranslationally modified microtubulesto methylmercury in differentiating embryonalcarcinoma-derived neurons.Toxicol. Appl. Pharmacol. 144, 215–224.PubMedGoogle Scholar
  57. Grandjean P and PJ Landrigan (2006) Developmental neurotoxicityof industrial chemicals.Lancet 368(9553), 2167–2178. E-pub 8 Nov. 2006.PubMedGoogle Scholar
  58. Grandjean P, PJ Jorgensen and P Weihe (1994) Human milkas a source of methylmercury exposure in infants.Environ.Health Perspect. 102, 74–77.PubMedGoogle Scholar
  59. Grandjean P, P Weihe, RF White, F Debes, S Araki, K Yokoyama, K Murata, N Sorensen, R Dahl and PJ Jorgensen(1997) Cognitive deficit in 7-year-old children with prenatalexposure to methylmercury.Neurotoxicol. Teratol. 19, 417–428.PubMedGoogle Scholar
  60. Grandjean P, P Weihe, RF White and F Debes (1998) Cognitiveperformance of children prenatally exposed to “safe” levelsof methylmercury.Environ. Res. 77, 165–172.PubMedGoogle Scholar
  61. Grandjean P, K Murata, E Budtz-Jorgensen and P Weihe (2004)Cardiac autonomic activity in methylmercury neurotoxicity:14-year follow-up of a Faroese birth cohort.J. Pediatr. 144, 169–176.PubMedGoogle Scholar
  62. Guidetti P, A Giacobazzi, P Zanoli and M Baraldi (1992)Prenatal exposure of rats to methylmercury: increasedsensitivity of the GABA-benzodiazepine receptor function, In:Metal Compounds in Environment and Life, Vol.4 (Merian E and W Haerdi, Eds.) (Northood, UK: Scienceand Technology Letters Chem Speciat. Bioavail.) Suppl. 4, 365–371.Google Scholar
  63. Gunderson VM, KS Grant-Webster, TM Burbacher and NK Mottet (1988) Visual recognition memory deficits in methylmercuryexposedMacacafascicularis infants.Neurotoxicol.Teratol. 10, 373–379.PubMedGoogle Scholar
  64. Gupta S (2001) Molecular steps of death receptor and mitochondrialpathways of apoptosis.Life Sci. 69, 2957–2964.PubMedGoogle Scholar
  65. Hass U (2006) The need for developmental neurotoxicity studiesin risk assessment for developmental toxicity.Reprod.Toxicol. 22, 148–156.PubMedGoogle Scholar
  66. Haykal-Coates N, TJ Shafer, WR Mundy and S Barone Jr(1998) Effects of gestational methylmercury exposure onimmunoreactivity of specific isoforms of PKC and enzymeactivity during post-natal development of the rat brain.BrainRes. Dev. Brain Res. 109, 33–49.Google Scholar
  67. Heidemann SR, P Lamoureux and WD Atchison (2001)Inhibition of axonal morphogenesis by nonlethal, submicromolarconcentrations of methylmercury.Toxicol. Appl.Pharmacol. 174, 49–59.PubMedGoogle Scholar
  68. Hock C, G Drasch, S Golombowski, F Muller-Spahn, B Willershausen-Zonnchen, P Schwarz, U Hock, JH Growdon and RM Nitsch (1998) Increased blood mercury levels in patients with Alzheimer’s disease.J. Neural. Transm. 105, 59–68.PubMedGoogle Scholar
  69. Hohmann CF and J Berger-Sweeney (1998) Cholinergic regulationof cortical development and plasticity. New twists toan old story.Perspect. Dev. Neurobiol. 5, 401–425.PubMedGoogle Scholar
  70. Hughes WL (1957) Aphysiochemical rationale for the biologicalactivity of mercury and its compounds. Ann.NY Acad.Sci. 65, 454–460.Google Scholar
  71. Johansson C, R Tofighi, C Tamm, M Goldoni, A Mutti and S Ceccatelli (2006) Cell death mechanisms in AtT20 pituitarycells exposed to polychlorinated biphenyls (PCB 126 andPCB 153) and methylmercury.Toxicol. Lett. 167, 183–190.PubMedGoogle Scholar
  72. Juarez BI, H Portillo-Salazar, R Gonzalez- Amaro, P Mandeville, JR Aguirre and ME Jimenez (2005) Participation of N-methyl-D-aspartate receptors on methylmercury-induced DNAdamage in rat frontal cortex.Toxicology 207, 223–229.PubMedGoogle Scholar
  73. Kakita A, K Wakabayashi, M Su, Y Yoneoka, M Sakamoto, F Ikuta and H Takahashi (2000) Intrauterine methylmercuryintoxication. Consequence of the inherent brain lesions andcognitive dysfunction in maturity.Brain Res. 877, 322–330.PubMedGoogle Scholar
  74. Kalil K and EW Dent (2005) Touch and go: guidance cues signalto the growth cone cytoskeleton.Curr. Opin. Neurobiol. 15, 521–526.PubMedGoogle Scholar
  75. Kaur P, M Aschner and T Syversen (2006) Glutathionemodulation influences methyl mercury induced neurotoxicityin primary cell cultures of neurons and astrocytes.Neurotoxicology 27, 492–500.PubMedGoogle Scholar
  76. Kienast T and A Heinz (2006) Dopamine and the diseasedbrain.CNS Neurol. Disord. Drug Targets 5, 109–131.PubMedGoogle Scholar
  77. Kim CY, K Nakai, Y Kasanumaand, H Satoh (2000) Comparisonof neurobehavioral changes in three inbred strains of miceprenatally exposed to methylmercury.Neurotoxicol. Teratol. 22, 397–403.PubMedGoogle Scholar
  78. Komuro H and P Rakic (1998) Orchestration of neuronalmigration by activity of ion channels, neurotransmitterreceptors, and intracellular Ca2+ fluctuations.J. Neurobiol. 37, 110–130.PubMedGoogle Scholar
  79. Kunimoto M (1994) Methylmercury induces apoptosis of ratcerebellar neurons in primary culture.Biochem. Biophys.Res. Commun. 204, 310–317.PubMedGoogle Scholar
  80. Kunimoto M and T Suzuki (1997) Migration of granule neuronsin cerebellar organotypic cultures is impaired by methylmercury.Neurosci. Lett. 226, 183–186.PubMedGoogle Scholar
  81. Landrigan PJ, B Sonawane, RN Butler, L Trasande, R Callanand D Droller (2005) Early environmental origins of neurodegenerativedisease in later life.Environ. Health Perspect. 113, 1230–1233.PubMedGoogle Scholar
  82. Lapham LW, E Cernichiari, C Cox, GJ Myers, RB Baggs, CF Shamlaye, PW Davidson and TW Clarkson (1995) An analysisof autopsy brain tissue from infants prenatally exposed tomethylmercury.Neurotoxicology 16, 689–704.PubMedGoogle Scholar
  83. Lärkfors L, A Oskarsson, J Sundberg and T Ebendal (1991)Methylmercury induced alterations in the nerve growth factorlevel in the developing brain.Brain Res. Dev. Brain Res. 62, 287–291.PubMedGoogle Scholar
  84. Levine RR, NJM Birdsall and NM Nathanson, editors (2001) Proc. 9th Intl. Symposium on Subtypes of MuscarinicReceptors.Life Sci. 68, 2449–2642.Google Scholar
  85. Levy OA, JJ Lah and AI Levey (2002) Notch signaling inhibitsPC12 cell neurite outgrowthvia RBP-J-dependent and-independent mechanisms.Dev. Neurosci. 24, 79–88.PubMedGoogle Scholar
  86. Lewandowski TA, RA Ponce, JS Charleston, S Hong and EM Faustman (2003) Effect of methylmercury on midbrain cellproliferation during organogenesis: potential cross-speciesdifferences and implications for risk assessment.Toxicol.Sci. 75, 124–133.PubMedGoogle Scholar
  87. Limke TL, SR Heidemann and WD Atchison (2004a)Disruption of intraneuronal divalent cation regulation bymethylmercury: are specific targets involved in alteredneuronal development and cytotoxicity in methylmercurypoisoning?NeuroToxicol. 25, 714–760.Google Scholar
  88. Limke TL, JJ Bearss and WD Atchison (2004b) Acute exposureto methylmercury causes Ca2+ dysregulation andneuronal death in rat cerebellar granule cells through an M3muscarinic receptor-linked pathway.Toxicol. Sci. 80, 60–68.PubMedGoogle Scholar
  89. Lindström H, J Luthman, A Oskarsson, J Sundberg and L Olson(1991) Effects of long-term treatment with methylmercuryon the developing rat brain.Environ. Res. 56, 158–169.PubMedGoogle Scholar
  90. Mamby DG (2001) Perspectives on object-recognition memoryfollowing hippocampal damage: lessons from studies in rats.Behav. Brain Res. 127, 159–181.Google Scholar
  91. Markowski VP, CB Flaugher, RB Baggs, RC Rawleigh, C Coxand B Weiss (1998) Prenatal and lactational exposure tomethylmercury affects select parameters of mouse cerebellardevelopment.Neurotoxicology 19, 879–892.PubMedGoogle Scholar
  92. Marty MS and WD Atchison (1997) Pathways mediatingCa2+ entry in rat cerebellar granule cells followingin vitroexposure to methyl mercury.Toxicol. Appl. Pharmacol. 147, 319–330.PubMedGoogle Scholar
  93. Marty MS and WD Atchison (1998) Elevations of intracellularCa2+ as a probable contributor to decreased viability in cerebellargranule cells following acute exposure to methylmercury.Toxicol. Appl. Pharmacol. 150, 98–105.PubMedGoogle Scholar
  94. McAllister AK (2002) Conserved cues for axon and dendritegrowth in the developing cortex.Neuron 33, 2–4.PubMedGoogle Scholar
  95. McKeown-Eyssen GE, J Ruedy and A Neims (1983) Methylmercury exposure in northern Quebec, II. Neurologic findingsin children.Am. J. Epidemiol. 118, 470–479.PubMedGoogle Scholar
  96. Miura K, N Koide, S Himeno, I Nakagawa and N Imura (1999)The involvement of microtubular disruption in methylmercury-inducedapoptosis in neuronal and nonneuronal celllines.Toxicol. Appl. Pharmacol. 160, 279–288.PubMedGoogle Scholar
  97. Miyamoto K, H Nakanishi, S Moriguchi, N Fukuyama, K Eto, J Wakamiya, K Murao, K Arimura and M Osame (2001)Involvement of enhanced sensitivity of N-methyl-D-aspartatereceptors in vulnerability of developing cortical neuronsto methylmercury neurotoxicity.Brain Res. 901, 252–258.PubMedGoogle Scholar
  98. Mori K, K Yoshida, S Oshikawa, S Ito, M Yoshida, M Satohand C Watanabe (2006) Effects of perinatal exposure to lowdoses of cadmium or methylmercury on thyroid hormonemetabolism in metallothionein-deficient mouse neonates.Toxicology 228, 77–84.PubMedGoogle Scholar
  99. Mundy WR and TM Freudenrich (2000) Sensitivity of immatureneurons in culture to metal-induced changes in reactive oxygenspecies and intracellular free calcium.Neurotoxicology 21, 1135–1144.PubMedGoogle Scholar
  100. Murata K, P Weihe, S Araki, E Budtz-Jorgensen and P Grandjean (1999) Evoked potentials in Faroese childrenprenatally exposed to methylmercury.Neurotoxicol. Teratol. 21, 471–472.PubMedGoogle Scholar
  101. Murata K, P Weihe, E Budtz-Jorgensen, PJ Jorgense andP Grandjean (2004) Delayed brainstem auditory evokedpotential latencies in 14-year-old children exposed to methylmercury.J. Pediatr. 144, 177–183.PubMedGoogle Scholar
  102. Myers GJ, PW Davidson, C Cox, CF Shamlaye, D Palumbo, E Cernichiari, J Sloane-Reeves, GE Wilding, J Kost, LS Huang and TW Clarkson (2003) Prenatal methylmercuryexposure from ocean fish consumption in the Seychelleschild development study.Lancet 361, 1686–1692.PubMedGoogle Scholar
  103. Nagashima K (1997) A review of experimental methylmercurytoxicity in rats: neuropathology and evidence for apoptosis.Toxicol. Pathol. 25, 624–631.PubMedGoogle Scholar
  104. Nagashima K, Y Fujii, T Tsukamoto, S Nukuzuma, M Satoh, M Fujita, Y Fujioka and H Akagi (1996) Apoptotic processof cerebellar degeneration in experimental methylmercuryintoxication of rats.Acta Neuropathol. 91, 72–77.PubMedGoogle Scholar
  105. Newland MC and EB Rasmussen (2000) Aging unmasksadverse effects of gestational exposure to methylmercury inrats.Neurotoxicol. Teratol. 22, 819–828.PubMedGoogle Scholar
  106. Nordenhäll K, L Dock and M Vahter (1998) Transplacentaland lactational exposure to mercury in hamster pups aftermaternal administration of methylmercury in late gestation.Pharmacol. Toxicol. 77, 130–135.Google Scholar
  107. NRC (2000)Toxicological Effects of Methylmercury (National Academy Press:Washington, DC).Google Scholar
  108. Ollinger K and UT Brunk (1995) Cellular injury induced byoxidative stress is mediated through lysosomal damage.Free Radic. Biol. Med. 19, 565–574.PubMedGoogle Scholar
  109. Onishchenko N, C Tamm, M Vahter, T Hokfelt, JA Johnson,DA Johnson and S Ceccatelli. (2007) Developmentalexposure to methylmercury alters learning and inducesdepression-like behavior in male mice.Toxicol. Sci. doi:10.1093/toxsci/kfl199Google Scholar
  110. Orrenius S, B Zhivotovsky and P Nicotera (2003) Regulationof cell death: the calcium-apoptosis link.Mol. Cell Biol. 4, 552–565.Google Scholar
  111. Oskarsson A, A Schultz, S Skerfving, IP Hallen, B Ohlinand BJ Lagerkvist (1996) Total and inorganic mercury inbreast milk in relation to fish consumption and amalgamin lactating women.Arch. Environ. Health 51, 234–241.PubMedGoogle Scholar
  112. Park ST, KT Lim, YT Chung and SU Kim (1996)Methylmercury-induced neurotoxicity in cerebral neuronculture is blocked by antioxidants and NMDA receptorantagonists.Neurotoxicology 17, 37–45.PubMedGoogle Scholar
  113. Parran DK, WR Mundy and S Barone Jr (2001) Effects ofmethylmercury and mercuric chloride on differentiationand cell viability in PC12 cells.Toxicol. Sci. 59, 278–290.PubMedGoogle Scholar
  114. Parran DK, S Barone Jr and WR Mundy (2003)Methylmercury decreases NGF-induced TrkA autophos-phorylationand neurite outgrowth in PC 12 cells.BrainRes. Dev. Brain Res. 141, 71–81.Google Scholar
  115. Peckham NH and BH Choi (1988) Abnormal neuronaldistribution within the cerebral cortex after prenatalmethylmercury intoxication.Acta Neuropathol. (Berl.) 76, 222–226.Google Scholar
  116. Philbert MA, ML Billingsley and KR Reuhl (2000)Mechanisms of injury in the central nervous system.Toxicol. Pathol. 28, 43–53.PubMedGoogle Scholar
  117. Ponce RA, TJ Kavanagh, NK Mottet, SG Whittaker and EM Faustman (1994) Effects of methyl mercury on the cellcycle of primary rat CNS cellsin vitro. Toxicol. Appl.Pharmacol. 127, 83–90.Google Scholar
  118. Rajanna B and M Hobson (1985) Influence of mercury onuptake of [3H]dopamine and [3H]norepinephrine by ratbrain synaptosomes.Toxicol. Lett. 27, 7–14.PubMedGoogle Scholar
  119. Rasmussen EB and MC Newland (2001) Developmentalexposure to methylmercury alters behavioral sensitivityto D-amphetamine and pentobarbital in adult rats.Neurotoxicol. Teratol. 23, 45–55.PubMedGoogle Scholar
  120. Rice DC (1996) Evidence for delayed neurotoxicity producedby methylmercury.Neurotoxicol. 17(3–4): 583–596.Google Scholar
  121. Rice DC (1998) Age-related increase in auditory impairmentin monkeysexposedin utero plus postnatally tomethylmercury.Toxicol. Sci. (2), 191–196.Google Scholar
  122. Rice D and S Barone Jr (2000) Critical periods of vulnerabilityfor the developing nervous system: evidence fromhumans and animal models.Environ. Health Perspect. 108, S3, 511–533.Google Scholar
  123. Rice DC and SG Gilbert (1990) Effects of developmentalexposure to methylmercury on spatial and temporalvisual function in monkeys.Toxicol. Appl. Pharmacol. 102, 151–163.PubMedGoogle Scholar
  124. Roegge CS, JR Morris, S Villareal, VC Wang, BE Powers, AY Klintsova, WT Greenough, IN Pessah and SL Schantz (2006) Purkinje cell and cerebellar effects followingdevelopmental exposure to PCBs and/or MeHg.Neurotoxicol. Teratol. 28, 74–85.PubMedGoogle Scholar
  125. Rossi AD, E Ahlbom, SO Ögren, P Nicotera and S Ceccatelli (1997) Prenatal exposure to methylmercuryalters locomotor activity of male but not female rats.Exp.Brain Res. 117, 428–436.PubMedGoogle Scholar
  126. Sager PR, RA Doherty and JB Olmsted (1983) Interactionof methylmercury with microtubules in cultured cells andin vitro. Exp. Cell. Res. 146, 127–137.Google Scholar
  127. Sager PR, M Aschner and PM Rodier (1984) Persistent,differential alterations in developing cerebellar cortexof male and female mice after methylmercury exposure.Brain Res. 314, 1–11.PubMedGoogle Scholar
  128. Sakamoto M, N Ikegami and A Nakano (1996) Protectiveeffects of Ca2+ channel blockers against methyl mercurytoxicity.Pharmacol. Toxicol. 78, 193–199.PubMedGoogle Scholar
  129. Sakamoto M, A Kakita, K Wakabayashi, H Takahashi, A Nakano and H Akagi (2002) Evaluation of changes inmethylmercury accumulation in the developing rat brainand its effects: a study with consecutive and moderatedose exposure throughout gestation and lactation periods.Brain Res. 949, 51–59.PubMedGoogle Scholar
  130. Sakamoto M, A Kakita, R Bezerra de Oliveira, HS Pan andH Takarashi (2004) Dose-dependent effects of methylmercuryadministered during neonatal brain spurt in rats.Dev. Brain Res. 152, 171–176.Google Scholar
  131. Sakaue M, M Okazaki and S Hara (2005) Very low levels ofmethylmercury induce cell death of cultured rat cerebel-larneuronsvia calpain activation.Toxicology 213(1–2), 97–106.PubMedGoogle Scholar
  132. Sarafian TA (1993) Methyl mercury increases intracellularCa2+ and inositol phosphate levels in cultured cerebellargranule neurons.J. Neurochem. 61, 648–657.PubMedGoogle Scholar
  133. Sarafian TA and MA Verity (1991) Oxidative mechanismsunderlying methyl mercury neurotoxicity.Int. J. Dev.Neurosci. 9, 147–153.PubMedGoogle Scholar
  134. Schantz SL and JJ Widholm (2001) Cognitive effectsof endocrine-disrupting chemicals.Environ. HealthPerspect. 109, 1197–1206.Google Scholar
  135. Shanker G and M Aschner (2003) Methylmercury-inducedreactive oxygen species formation in neonatal cerebralastrocytic cultures is attenuated by antioxidants.BrainRes. Mol. Brain Res. 110, 85–91.Google Scholar
  136. Shanker G, JL Aschner, T Syversen and M Aschner (2004)Free radical formation in cerebral cortical astrocytesin culture induced by methylmercury.Brain Res. Mol.Brain Res. 10, 48–57.Google Scholar
  137. Shanker G, T Syversen, JL Aschner and M Aschner (2005)Modulatory effect of glutathione status and antioxidantson methylmercury-induced free radical formation inprimary cultures of cerebral astrocytes.Brain Res. Mol.Brain Res. 137, 11–22.PubMedGoogle Scholar
  138. Sirois JE and WD Atchison (2000) Methylmercury affectsmultiple subtypes of calcium channels in rat cerebellargranule cells.Toxicol. Appl. Pharmacol. 167, 1–11.PubMedGoogle Scholar
  139. Skaper SD (2005) Neuronal growth-promoting and inhibitorycues in neuroprotection and neuroregeneration.Ann.NYAcad. Sci. 1053, 376–385.Google Scholar
  140. Spurgeon A (2006) Prenatal methylmercury exposure anddevelopmental outcomes: review of the evidence and discussionof future directions.Environ. Health Perspect. 114, 307–312.PubMedGoogle Scholar
  141. Stringari J, FC Meotti, DO Souza, ARS Santos and M Farina (2006) Postnatal methylmercury exposure induceshyperlocomotor activity and cerebellar oxidative stressin mice: dependence on the neurodevelopmental period.Neurochem. Res. 31, 563–569.PubMedGoogle Scholar
  142. Szasz A, B Barna, Z Szupera, G De Visscher, Z Galbacss, M Kirsch-Volders and M Szente (1999) Chronic low-dosematernal exposure to methylmercury enhancesepileptogenicity in developing rats.Int. J. Dev. Neurosci. 17, 733–742.PubMedGoogle Scholar
  143. Tamm C, J Duckworth, O Hermanson and S Ceccatelli(2006) High susceptibility of neural stem cells to methylmercurytoxicity: effects on cell survival and neuronaldifferentiation.J. Neurochem. 97, 69–78PubMedGoogle Scholar
  144. Thompson SA, CC White, CM Krejsa, DL Eaton and TJ Kavanagh (2000) Modulation of glutathione and glutamate-L-cysteineligase by methylmercury during mousedevelopment.Toxicol. Sci. 57, 141–146.PubMedGoogle Scholar
  145. Tofighi R, C Johansson, M Goldoni, MV Vettori, A Muttiand S Ceccatelli (2006) Hippocampal neurons undergoapoptotic and necrotic cell death after exposure to methylmercury,PCB 153 and PCB 126.Toxicol. Lett. 164S, S207 (Abstr.).Google Scholar
  146. Toimela T and H Tahti (2004) Mitochondrial viabilityand apoptosis induced by aluminum, mercuric mercuryand methylmercury in cell lines of neural origin.Arch.Toxicol. 78, 565–574.PubMedGoogle Scholar
  147. Usuki F, A Yasutake, F Umehara, H Tokunaga, M Matsumoto, K Eto, S Ishiura and I Higuchi (2001)Invivo protection of a water-soluble derivative of vitaminE, Trolox, against methylmercury-intoxication in the rat.Neurosci. Lett. 304, 199–203.PubMedGoogle Scholar
  148. Vahter M, NK Mottet, L Friberg, B Lind, DD Shen and T Burbacher (1994) Speciation of mercury in the primateblood and brain following long-term exposure to methylmercury.Toxicol. Appl. Pharmacol. 124, 221–229.PubMedGoogle Scholar
  149. Vahter M, A Akesson, B Lind, U Bjors, A Schutz and M Berglund (2000) Longitudinal study of methylmercuryand inorganic mercury in blood and urine of pregnantand lactating women, as well as in umbilical cord blood.Environ. Res. 84, 186–194.PubMedGoogle Scholar
  150. Vahter M, A Åkesson, C Lidén, S Ceccatelli and M Berglund (2006) Gender differences in the dispositionand toxicity of metals.Environ. Res. 2006 Sep. 20; [Epubahead of print].Google Scholar
  151. Vicente E, M Boer, M Leite, M Silva, F Tramontina, L Porciuncula, C Dalmaz and C-A Goncalves (2004a)Cerebrospinal fluid S100B increases reversibly in neonatesof methyl mercury-intoxicated pregnant rats.Neurotoxicology 25, 771–777.PubMedGoogle Scholar
  152. Vicente E, M Boer, C Netto, C Fochesatto, C Dalmaz, I Rodrigues Siqueira and C-A Goncalves (2004b)Hippocampal antioxidant system in neonates frommethylmercury-intoxicated rats.Neurotoxicol. Teratol. 26, 817–823.PubMedGoogle Scholar
  153. Vilagi I, J Doczi and I Banczerowski-Pelyhe (2000) Alteredelectrophysiological characteristics of developing ratcortical neurones after chronic methylmercury chloridetreatment.Int. J. Dev. Neurosci. 18, 493–499.PubMedGoogle Scholar
  154. Vogel DG, RL Margolis and NK Mottet (1985) The effectsof methyl mercury binding to microtubules.Toxicol.Appl. Pharmacol. 80, 473–486.PubMedGoogle Scholar
  155. Waetzig V and T Herdegen (2003) The concerted signalingof ERK1/2 and JNKs is essential for PC12 cell neurito-genesisand converges at the level of target proteins.Mol.Cell Neurosci. 24, 238–249.PubMedGoogle Scholar
  156. Wagner GC, KR Reuhl, X Ming and AK Halladay (2006)Behavioral and neurochemical sensitization to amphetaminefollowing early postnatal administration of methylmercury(MeHg).Neurotoxicol. 28(1), 59–66. Epub2006 Jul 21.Google Scholar
  157. Wakabayashi K, A Kakita, M Sakamoto, M Su, K Iwanagaand F Ikuta (1995) Variability of brain lesions in ratsadministered methylmercury at various postnatal developmentalphases.Brain Res. 705, 267–272.PubMedGoogle Scholar
  158. Watanabe C and H Satoh (1996) Evolution of our understandingof methylmercury as a heath threat.Environ.Health Perspect. 104, 367–379.PubMedGoogle Scholar
  159. Watanabe C, K Yoshida, Y Kasanuma, Y Kun and H Satoh (1999a)In utero methylmercury exposure differentiallyaffects the activities of selenoenzymes in the fetal mousebrain.Environ. Res. Sect. A. 80, 208–214.Google Scholar
  160. Watanabe C, Y Kasanuma, Y Dejima and H Satoh (1999b)The effect of prenatal methylmercury exposure on theGSH level and lipid peroxidation in the fetal brain andplacenta. Tohoku.J. Exp. Med. 187, 121–126.Google Scholar
  161. Weiss B, W Thomas, TW Clarkson and W Simon (2002)Silent latency periods in methylmercury poisoning andin neurodegenerative disease.Environ. Health Perspect. 110, 851–854.PubMedGoogle Scholar
  162. Whitaker-Azmitia PM, X Zhang and C Clarke (1994) Effectsof gestational exposure to monoamine oxidase inhibitorsin rats: preliminary behavioural and neurochemical studies.Neuropsycopharmacology 11, 125–132.Google Scholar
  163. Whitford KL, V Marillat, E Stein, CS Goodman, M Tessier-Lavigne, A Chedotal and A Ghosh (2002) Regulation ofcortical dendrite development by Slit-Robo interactions.Neuron 33, 47–61.PubMedGoogle Scholar
  164. Widholm JJ, S Villareal, RF Seegal and SL Schantz (2004)Spatial alternation deficits following developmentalexposure to Aroclor 1254 and/or methylmercury in rats.Toxicol. Sci. 82, 577–589.PubMedGoogle Scholar
  165. Wilke RA, CP Kolbert, RA Rahimi and AJ Windebank(2003) Methylmercury induces apoptosis in culturedrat dorsal root ganglion neurons.Neurotoxicology 24, 369–378.PubMedGoogle Scholar
  166. Wilson DT, MA Polunas, R Zhou, AK Halladay, HE Lowndesand KR Reuhl (2005) Methylmercury alters Eph and ephrinexpression during neuronal differentiation of P19 embryonalcarcinoma cells.Neurotoxicology 26, 661–674.PubMedGoogle Scholar
  167. Xue F, C Holzman, M Hossein Rahbar, K Trosko and L Fischer (2007) Maternal fish consumption, mercury levelsand risk of preterm delivery.Environ. Health Perspect. 115, 42–47.PubMedGoogle Scholar
  168. Yee S and BH Choi (1994) Methylmercury poisoning inducesoxidative stress in the mouse brain.Exp. Mol. Pathol. 60, 188–196.PubMedGoogle Scholar
  169. Zanoli P, C Truzzi, C Veneri, D Braghiroli and M Baraldi(1994) Methyl mercury during late gestation affects temporarilythe development of cortical muscarinic receptors inrat offspring.Pharmacol. Toxicol. 75, 261–264.PubMedGoogle Scholar
  170. Zanoli P, C Truzzi, C Veneri, D Brandoli and M Baraldi(1997) Prenatal exposure to methylmercury during lategestation affects cerebral opiatergic system in rat offspring.Environ. Res. 74, 48–53.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Carolina Johansson
    • 1
    Email author
  • Anna F. Castoldi
    • 2
  • Natalia Onishchenko
    • 1
  • Luigi Manzo
    • 2
    • 3
  • Marie Vahter
    • 4
  • Sandra Ceccatelli
    • 1
  1. 1.Division of Toxicology and Neurotoxicology, Institute of Environmental MedicineKarolinska InstitutetStockholmSweden
  2. 2.IRCCS Salvatore Maugeri Foundation, Toxicology DivisionInstitute of PaviaPaviaItaly
  3. 3.Department of Internal Medicine and Therapeutics, Toxicology DivisionUniversity ofPaviaPaviaItaly
  4. 4.Division of Metal Toxicology, Institute of Environmental MedicineKarolinska InstitutetStockholmSweden

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