题名

Autism and Parkinson's Disease: Animal Models and a Common Etiological Mechanism

DOI

10.4077/CJP.2009.AMH081

作者

Carrie L. Yochum;George C. Wagner

关键词

animal models ; autism ; Parkinson's disease ; reactive oxygen species ; antioxidants

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

52卷4期(2009 / 08 / 01)

页次

236 - 249

内容语文

英文

英文摘要

Autism is a behaviorally-defined neurodevelopmental disorder that is difficult to diagnose, treat, and study due to its unknown etiology, widely varying symptoms, and lack of an identified neuropathology. In contrast, Parkinson's disease is a neurodegenerative disease of unknown etiology that is well defined both behaviorally and neuropathologically. While clinically these two disorders appear to have little in common, we would like to present the hypothesis that their respective etiologies may share similar features. Both autism and Parkinson's disease are thought to be the result of interactions between environmental insult, genetic polymorphisms, and age. In addition, since no particular environmental toxicant has been identified as causal for either condition, we propose that any of a number of possible environmental toxicants interact with the individual's genetic sensitivity to cause the underlying neuronal damage. We suggest that while low levels of exposure to any of these individual toxicants may be well-tolerated by most individuals during early development, various combinations of the toxicants may exert a cumulative, deleterious effect. Likewise, although several genes have been linked to autism and Parkinson's disease, respectively, no single gene has been identified that can account for a majority of cases for either. Therefore, various combinations of genetic alterations predispose individuals to their respective disorders but it remains the case that the environmental exposure(s) must occur during critical periods of development for the eventual disease manifestation. The objective of this review is to provide examples from animal models that the etiologies of autism and Parkinson's disease have common features of toxicant-induced oxidative stress together with genetic deficiencies in the ability to manage reactive oxygen species and, furthermore, that therapeutic intervention using antioxidants delivered at the time of toxicant exposure may be beneficial for both.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Allen, G.,Muller, R.A.,Courchesne, E.(2004).Cerebellar function in autism: functional magnetic resonance imaging activation during a simple motor task.Biol. Psychi.,56,269-278.
  2. Ardinger, H.H.,Atkin, J.F.,Blackston, R.D.,Elsas, L.J.,Clarren, S.K.,Livingstone, S.,Flannery, D.B.,Pellock, J.M.,Harrod, M.J.,Lammer, E.J.(1988).Verification of the fetal valproate synbdrome phenotype.Am. J. Med. Gen.,29,171-185.
  3. Armstrong, R.N.(1997).Structure, catalytic mechanism and evolution of the glutathione transferases.Chem. Res. Toxicol.,10,2-18.
  4. Aschner, M.,Yao, C.P.,Allen, J.W.,Tan, K.H.(2000).Methylmercury alters glutamate transport in astrocytes.Neurochem. Int.,37,199-206.
  5. Axt, K.J,Commins, D.L,Vosmer, G.,Seiden, L.S.(1990).Alpha-Methyl-p-tyrosine pretreatment partially prevents METH-induced endogenous neurotoxin formation.Brain Res.,515,269-276.
  6. Aylward, E.H.,Minshew, N.J.,Field, K.,Sparks, B.F.,Singh, N.(2002).Effects of age on brain volume and head circumference in autism.Neurology,59,175-183.
  7. Aylward, E.H.,Minshew, N.J.,Goldstein, G.,Honeycutt, N.A.,Augustine, A.M.,Yates, K.O.,Barta, P.E.,Pearlson, G.D.(1999).MRI volumes of the amygdala and hippocampus in non-mentally retarded autistic adolescents and adults.Neurology,53,2145-2150.
  8. Baba, Y.,Markopoulou, K.,Putzke, J.D.,Whaley, N.R.,Farrer, M.J.,Wszolek, Z.K.,Uitti, R.J.(2006).Phenotypic commonalities in familial and sporadic parkinson disease.Arch. Neurology,63,579-583.
  9. Bailey, A.,Phillips, W.,Rutter, M.(1996).Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives.J. Child Psychol. Psychi.,37,89-126.
  10. Bains, J.S.,Shaw, C.A.(1997).Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death.Brain Res.,25,335-358.
  11. Barbeau, A.(1984).Etiology of Parkinson's disease: A research strategy.Can. J. Neurol. Sci.,11,24-28.
  12. Bauman, M.L.,Kemper, T.L.(1985).Histoanatomic observations of the brain in early infantile autism.Neruology,35,866-874.
  13. Bernard, S.,Enayati, A.,Redwood, L.,Roger, H.,Binstock, T.(2000).Autism: A novel form of mercury poisoning.ARC Res..
  14. Bertrand, J.,Mars, A.,Boyle, C.,Bove, F.,Yeargin-Allsopp, M.,Decoufle, P.(2001).Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation.Pediatrics,108,1155-1161.
  15. Board, P.G.(2007).The use of glutathione transferase-knockout mice as pharmacological and toxicological models.Expert Opinion Drug Met. Toxicol.,3,421-433.
  16. Bonifati, V.,De Michele, G.,Lucking, C. B.,Durr, A.,Fabrizio, E.,Ambrosio, G.,Vanacore, N.,De Mari, M.,Marconi, R.,Capus, L.,Breteler, M.M.B.,Gasser, T.,Oostra, B.,Wood, N.,Agid, Y.,Filla, A.,Meco, G.,Brice, A.(2001).The parkin gene and its phenotype.Neurol. Sci.,22,51-52.
  17. Carver, J.A.,Rekas, A.,Thorn, D.C.,Wilson, M.R.(2003).Small heatshock proteins and clusterin: intra-and extracellular molecular chaperones with a common mechanism of action and function?.IUBMB Life,55,661-668.
  18. Chapman, J.B.,Cutler, M.G.(1984).Sodium valproate: effects on social behaviour and physical development in the mouse.Psychopharmacology (Berl),83,390-396.
  19. Chauhan, A.,Chauham, V.,Brown, W.T.,Cohen, I.(2004).Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferring-the antioxidant proteins.Life Sci.,75,2539-2549.
  20. Commins, D.L.,Axt, K.J.,Vosmer, G.,Seiden, L.S.(1987).5,6-Dihydroxytryptamine, a serotonergic neurotoxin, is formed endogenously in the rat brain.Brain Res.,403,7-14.
  21. Cotariu, D.,Evans, S.,Zaidman, J.L.,Marcus, O.(1990).Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid.Biochem. Pharmacol,40,589-593.
  22. Courchesne, E.,Karns, C.M.,Davis, H.R.,Ziccardi, R.,Carper, R.A.,Tigue, Z.D.,Chisum, H.J.,Moses, P.,Pierce, K.,Lord, C.,Lincoln, A.J.,Pizzo, S.,Schreibman, L.,Haas, R.H.,Akshoofoff, N.A.,Courchesne, R.Y.(2001).Unusual brain growth patterns in early life in patients with autistic disorder: and MRI study.Neurology,57,245-254.
  23. Coutinho, A.M.,Sousa, I.,Martins, M.,Correia, C.,Morgadinho, T.,Bento, C.,Marques, C.,Ataííde A.,Miguel, T.S.,Moore, J.H.,Guiomar Oliveira, G.,Vicente A.M.(2007).Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels.Hum. Gen.,121,243-256.
  24. Daniels, W.W.,Warren, R.P.,Odell, J.D.,Maciulis, A.,Burger, R.A.,Warren, W.L.,Torres, A.R.(1995).Increased frequency of the extended or ancestral haplotype B44-SC30-DR4 in autism.Neuropsychobiology,32,120-123.
  25. Darios, F.,Corti, O.,Lucking, C.B.,Hampe, C.,Muriel, M.P.,Abbas, N.,Gu, W.J.,Hirsch, E.C.,Rooney, T.,Ruberg, M.,Brice, A.(2003).Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death.Hum. Mol. Gen.,12,517-526.
  26. Dawson, J.E.,Raymond, A.M.,Winn, L.M.(2006).Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice.Toxicol. App. Pharmacol.,221,124-132.
  27. de la Fuente-Fernandez, R.(2000).Maternal effect on Parkinson's disease.Ann. Neurol.,48,782-787.
  28. De Vito, M.J.,Wagner, G.C.(1998).METH-induced neuronal damage: a possible role for free radicals.Neuropharmacology,28,1145-1150.
  29. Dexter, D.T.,Holley, A.E.,Flitter, W.D.,Slater, T.F.,Wells, F.R.,Daniel, S.E.,Lees, A.J.,Jenner, P.,Marsden, C.D.(1994).Increased levels of lipid peroxidation in the parkinsonian substantia nigra: an HPLC and ESR study.Movement Dis.,9,92-97.
  30. Dey, P.M.,Reuhl, K.R.(1999).Developmental methylmercury administration alters cerebellar PSA-NCAM expression and Golgi sialyltransferase activity.Brain Res.,845,139-151.
  31. Elsby, R.,Kitteringham, N.R.,Goldring, C.E.,Lovatt, C.A.,Chamberlain, M.,Henderson, C.J.,Wolf, C.R.,Park, B.K.(2003).Increased constitutive c-Jun N-terminal kinase signaling in mice lacking glutathione S-transferase Pi..J. Biol. Chem.,278,22243-22249.
  32. Eriksson, K.,Viinikainen, K.,Monkkonen, A.,Aikia, M.,Nieminen, P.,Heinonen, S.,Kalviainen, R.(2005).Children exposed to valproate in utero-Population based evaluation of risks and confounding factors for long-term neurocognative development.Epil. Res.,65,189-200.
  33. Folstein, S.E.,Rosen-Sheidley, B.(2001).Genetics of autism: complex aetiology for a heterogeneous disorder.Nat. Rev. Genet.,2,943-955.
  34. Fombonne, E.(2003).Epidemiological surveys of autism and other pervasive developmental disorders: an update.J. Autism Dev. Disord.,33,365-382.
  35. Forrester, M.B.,Merz, R.D.(2007).Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002.J. Toxicol. Environ. Health,70,7-18.
  36. Golan, H.M.,Lev, V.,Hallak, M.,Sorokin, Y.,Huleihel, M.(2005).Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy.Neuropharmacology,48,903-917.
  37. Graf, W.D.,Pippenger, C.E.,Shurtleff, D.B.(1995).Erythrocyte antioxidant enzyme activities in children with myelomeningocele.Dev. Med. Child Neurol.,37,900-905.
  38. Hatcher, J.M.,Richardson, J.R.,Guillot, T.S.,McCormack, A.L.,Di Monte, D.A.,Jones, D.P.,Pennell, K.D.,Miller, G.W.(2007).Dieldrin exposure induced oxidative damage in the mouse nigrostriatal dopamine system.Exp. Neurol.,204,619-630.
  39. Hazlett, H.C.,Poe, M.,Gerig, G.,Smith, R.G.,Provenzale, J.,Ross, A.,Gilmore, J.,Piven, J.(2005).Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years.Arch. Gen. Psychi.,62,1366-1376.
  40. Howard, M.A.,Cowell, P.E.,Boucher, J.,Broks, P.,Mayes, A.,Farrant, A.,Roberts, N.(2000).Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.Neuroreport,11,2931-2935.
  41. Imai, Y.,Soda, M.,Takahashi, R.(2000).Parkins upresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.J. Biol. Chem.,275,35661-35664.
  42. Ingram, J.L.,Peckharm, S.M.,Tisdale, B.,Rodier, P.M.O.(2000).Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism.Neurotoxicol. Teratol.,22,319-324.
  43. Jamain, S.,Betancur, C.,Quach, H.,Philippe, A.,Fellous, M.,Giros, B.,Gillberg, C.,Leboyer, M.,Bourgeron, T.(2002).Linkage and association of the glutamate receptor 6 gene with autism.Mol. Psychi.,7,302-310.
  44. James, S.J.,Cutler, P.,Melnyk, S.,Jernigan, S.,Janak, L.,Gaylor, D.W.,Neubrander, J.A.(2004).Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.Am. J. Clin. Nut.,80,1611-1617.
  45. Jenner, P.,Olanow, C.W.(1996).Oxidative stress and the pathogenesis of Parkinson's disease.Neurology,47,161-170.
  46. Johansson, A.S.,Stenberg, G.,Widersten, M.,Mannervik, B.(1998).Structure-activity relationships and thermal stability of human glutathione transferase P1-1 governed by the H-site residue 105.J. Mol. Biol.,278,687-698.
  47. Johnson, W.G.,Stenroos, E.S.,Spychala, J.R.,Chatkupt, S.,Ming, S.X.,Buyske, S.(2004).New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy.Am. J. Med. Genet.,124,339-345.
  48. Jurima-Romet, M.,Abbott, F.S.,Tang, W.,Huang, H.S.,Whitehouse, L.W.(1996).Cytotoxicity of unsaturated metabolites of valproic acid and protection by vitamins C and E in glutathionedepleted rat hepatocytes.Toxicology,112,69-85.
  49. Kanner, L.(1943).Autistic disturbances of affective contact.Nerv. Child,2,217-250.
  50. Kemper, T.L.,Bauman, M.(1998).Neuropathology of infantile autism.J. Neuropathol. Exp. Neurol.,57,645-652.
  51. Kern, J.K.,Jones, A.M.(2006).Evidence of toxicity, oxidative stress, and neuronal insult in autism.J. Toxicol. Environ. Health,9,485-499.
  52. Kita, T.,Wagner, G.C.,Nakashima, T.(2003).Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.J. Pharmacol. Sci.,92,178-195.
  53. Kitada, T.,Asakawa, S.,Hattori, N.,Matsumine, H.,Yamamura, Y.,Minoshima, S.,Yokochi, M.,Mizuno, Y.,Shimizu, N.(1998).Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.Nature,392,605-608.
  54. Klee, S.,Johanssen, S.,Ungemach, F.R.(2000).Evidence for a trigger function of valproic acid in xenobiotic-induced hepatotoxicity.Pharmacol. Toxicol.,87,89-95.
  55. Koch, S.,Jager-Roman, E.,Losche, G.,Nau, H.,Rating, D.,Helge, H.(1996).Antiepileptic drug treatment in pregnancy: drug side effects in the neonate and neurological outcome.Acta Paediatr.,85,739-746.
  56. Lam, K.S.L.,Aman, M.G.,Arnold, L.E.(2006).Neurochemical correlates of autistic disorder: a review of the literature.Res. Dev. Dis.,27,254-289.
  57. Lavedan, C.(1998).The synuclein family.Genome Res.,8,871-880.
  58. Marek, G.J.,Vosmer, G.,Seiden, L.S.(1990).Dopamine uptake inhibitors block long-term neurotoxic effects of METH upon dopaminergic neurons.Brain Res.,513,274-279.
  59. Matsui, A.,Ikeda, T.,Enomoto, K.,Hosoda, K.,Nakashima, H.,Omae, K.,Watanabe, M.,Hibi, T.,Kitajima, M.(2000).Increased formation of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, in human breast cancer tissue and its relationship to GSTP1 and COMT genotypes.Cancer Lett.,151,87-95.
  60. Mawer, G.,Clayton-Smith, J.,Coyle, H.,Kini, U.(2002).Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium valproate.Seizure,69,1-7.
  61. Meador, K.J.,Baker, G.A.,Finnell, R.H.,Kalayjian, L.A.,Liporace, J.D.,Loring, D.W.,Mawer, G.,Pennell, P.B.,Smith, J.C.,Wolff, M.C.(2006).In utero antiepileptic drug exposure.Neurology,67,407-412.
  62. Ming, X.,Brimacombe, M.,Chaaban, J.,Zimmerman-Bier, B.,Wagner, G.C.(2008).Autism spectrum disorders: concurrent clinical disorders.J. Child Neurol.,23,6-13.
  63. Ming, X.,Brimacombe, M.,Malek, J.H.,Jani, N.,Wagner, G.C.(2008).Autism spectrum disorders and identified toxic land fills: co-occurrence across States.Environ. Health Insights,2,55-59.
  64. Ming, X.,Cheh, M.A.,Yochum, C.L.,Halladay, A.K.,Wagner, G.C.(2008).Evidence of oxidative stress in autism derived from animal models.Am. J. Biochem. Biotech.,4,218-225.
  65. Ming, X.,Stein, T.P.,Johnson, W.G.,Lambert, G.H.,Wagner, G.C.(2005).Increased excretion of a lipid perodidation biomarker in autism.Prosta. Leuko. Essent Fatty Acids,73,379-384.
  66. Mitchell, S.L.,Kiely, D.K.,Kiel, D.P.,Lipsitz, L.A.(1996).The epidemiology, clinical characteristics, and natural history of older nursing home residents with a diagnosis of Parkinson's disease.J. Am. Geriatr. Soc.,44,394-399.
  67. Moore, S.J.,Turnpenny, P.,Quinn, A.,Glover, S.,Lloyd, D.J.,Montgomery, T.,Dean, J.C.S.(2000).A clinical study of 57 children with fetal anticonvulsant syndromes.J. Med. Gen.,3,489-497.
  68. Muhle, R.,Trentacoste, S.V.,Rapin, I.(2004).The genetics of autism.Pediatrics,113,472-486.
  69. Muller, R.-A.,Pierce, K.,Ambrose, J.B.,Allen, G.A.,Courchsne, E.(2001).Atypical patterns of cerebral motor activation in autism: a functional magnetic resonance study.Biol Psychi.,49,665-676.
  70. Mundy, W.R.,Freudenrich T.M.(2000).Sensitivity of immature neurons in culture to metalinduced changes in reactive oxygen species and intracellular free calcium.Neurotoxicology,21,1135-1144.
  71. Myers, G.J.,Davidson, P.W.(2000).Does methylmercury have a role in causing developmental disabilities in children? Environ.Health Perspect.,108,413-420.
  72. Na, L.,Wartenberg, M.,Heinz, N.,Hescheler, J.,Sauer, H.(2003).Anticonvulsant valproic acid inhibits cardiomyocyte differentiation of embryonic stem cells by increasing intracellular levels of reactive oxygen species.Birth Defects Res.,67,174-180.
  73. Olanow, C.W.,Tatton, W.G.(1999).Etiology and pathogenesis of Parkinson's disease.Ann. Rev. Neurosci.,22,123-144.
  74. O''Leary, V.B.,Parle-McDermott, A.,Molly, A.M.,Kirke, P.N.,Johnson, Z.,Conley, M.,Scott, J.M.,Mills, J.L.(2002).MTRR and MTHFR polymorphism: link to Down syndrome.Am. J. Med. Genet.,107,151-155.
  75. Oury, T.D.,Ho, Y.S.,Piantadosi, C.A.,Crapo, J.D.(1992).Extracellular superoxide dismutase, nitric oxide, and central nervous system O2 toxicity.Proc. Natl. Acad. Sci.,89,9715-9719.
  76. Park, S.T.,Lim, K.T.,Chung, Y.T.,Kim, S.U.(1996).Methylmercuryinduced neurotoxicity in cerebral neuron culture is blocked by antioxidants and NMDA receptor antagonists.Neurotoxicology,17,37.
  77. Pickles, A.,Bolton, P.,Macdonald, H.,Bailey, A.,Le Couteur, A.,Sim, C.H.,Rutter, M.(1995).Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism.Am. J. Hum. Genet.,57,717-726.
  78. Pippenger, C.E.,Meng, X.,Rothner, A.D.,Levy, R.H. (Eds.),Penry, J.K. (Eds)(1991).Idiosyncratic reactions to valproate: Clinical Risk Patterns and Mechanisms of Toxicity.New York:Raven Press.
  79. Piven, J.,Arndt, S.,Bailey, J.,Havercamp, S.,Andreasen, N.C.,Palmer, P.(1995).An MRI study of brain size in autism.Am. J. Psychi.,152,1145-1149.
  80. Purisai, M.G.,McCormack, A.L.,Langston, W.J.,Johnston, L.C.,Di Monte, D.A.(2005).Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates.Neurobiol. Dis.,20,898-906.
  81. Rekas, A.(2004).Interaction of the molecular chaperone "B-crystallin with"-synuclein: effects on the amyloid fibril formation and chaperone activity.J. Mol. Biol.,340,1167-1183.
  82. Rekas, A.,Adda, C.G.,Andrew, A.J.,Barnham, K.J.,Sunde, M.,Galatis, D.,Williamson, N.A.,Masters, C.L,Anders, R.F.,Robinson, C.V.,Cappai, R.,Carver, J.A.(1999).A genomic screen of autism: evidence for a multilocus etiology.Am. J. Hum. Gen.,65,493-507.
  83. Rice, D.,Barone, S.(2000).Critical periods of vulnerability for the developing nervous system: Evidence from human and animal models.Environ. Health Prospect.,108,511-533.
  84. Rice, D.C.(1996).Sensory and cognitive effects of developmental methylmercury exposure in monkeys and a comparison to effects in rodents.Neurotoxicology,17,139-154.
  85. Ritvo, E.R.,Freeman, B.J.,Scheibel, A.B.,Duong, T.,Robinson, H.,Guthrie, D.,Ritvo, A.(1986).Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLANSAC autopsy research report.Am. J. Psychi.,143,862-866.
  86. Rodier, P.M.,Hyman, S.L.(1998).Early environmental factors in autism.Mental Retardation and Developmental Disabilities Research Reviews,4,121-128.
  87. Saitoh, O.,Courchesne, E.,Egaas, B.,Lincoln, A.J.,Schreibman, L.(1995).Cross-sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalities.Neurology,45,317-324.
  88. Sanfeliu, C.,Sebastia, J.,Ki, S.U.(2001).Methylmercury neurotoxicity in cultures of human neurons, astrocytes, neuroblastoma cells.Neurotoxicology,22,317-327.
  89. Schain, R.J.,Freedman, D.X.(1961).Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.J. Pediatrics,58,351-320.
  90. Schneider, T.,Przewlocki, R.(2004).Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism.Neuropsychopharmacology.
  91. Seiden, L.S.,Vosmer, G.(1984).Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single large dose of methylamphetamine.Pharmacol. Biochem. Behav.,21,29-31.
  92. Shi, L.,Fatemi, H.,Sidwell, R.W.,Patterson, P.H.(2003).Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring.J. Neurosci.,23,297-302.
  93. Simon, G.,Moog, C.,Obert, G.(1994).Valproic acid reduces the intracellular level of glutathione and stimulates human immunodeficiency virus.Chem. Biol. Interact.,91,111-121.
  94. Sobaniec-Lotowweska, M.E.(2001).Ultrastructure of purkinje cell perikara and their dendritic processes in the rat cerebellar cortex in experimental encephalopathy induced by chronic application of valproate.Int. J. Exp. Pathol.,82,337-348.
  95. Sorg, O.,Schilter, B.,Honegger, P.,Monnet-Tschudi, F.(1998).Increased vulnerability of neurones and glial cells to low concentrations of methylmercury in a prooxidant situation.Acta Neuropathol. (Berl),96,621.
  96. Soto-Ares, G.,Joyes, B.,Lemaitre, M.P.,Vallee, L.,Pruvo, J.P.(2003).MRI in children with mental retardation.Pediatr. Radiol.,33,334-345.
  97. Sparks, B.F.,Friedman, S.D.,Shaw, D.W.,Aylward, E.H.,Echelard, D.,Artru, A.A.,Maravilla, K.R.,Giedd, J.N.,Munson, J.,Dawson, G.,Dager, S.R.(2002).Brain structural abnormalities in young children with autism spectrum disorder.Neurology,59,184-192.
  98. Stohs, S.J.,Bagchi, D.(1995).Oxidative mechanisms in the toxicity of metal ions.Free Rad. Biol. Med.,18,321.
  99. Sugie, Y.,Sugie, H.,Fukuda, T.,Ito, M.,Sasada, Y.,Nakabayashi, M.,Fukashiro, K.,Ohzeki, T.(2005).Clinical efficacy of fluvoxamine and functional polymorphism in a serotonin transporter gene on childhood autism.J. Autism Dev. Dis.,35,377-385.
  100. Tabatabaei, A.R.,Abbott, F.S.(1999).Assessing the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity.Chem. Res. Toxicol.,12,323-330.
  101. Tabatabaei, A.R.,Thies, R.L.,Farrell, K.,Abbott, F.S.(1997).A rapid in vitro assay for evaluation of metabolism-dependent cytotoxicity of antiepileptic drugs on isolated human lymphocytes.Fundam. Appl. Toxicol.,37,181-189.
  102. Tang, W.,Borel, A.G.,Abbott, F.S.(1996).Conjugation of glutathione with a toxic metabolite of valproic acid, (E)-2-propyl-2,4-pentadienoic acid, catalyzed by rat hepatic glutathione-Stransferases.Drug Metab. Disp.,24,436-446.
  103. Tong, V.,Chang, T.K.H.,Chen, J.,Abbotts, F.S.(2003).The effect of valproic acid on hepatic and plasma levels of 15-F2t-isoprostne in rats.Free Rad. Biol. Med.,34,1435-1446.
  104. Tuchman, R.F.,Rapin, I.(1997).Regression in pervasive developmental disorders: Seizures and epileptiform EEG correlates.Pediatrics,99,560-566.
  105. Twelves, D.,Perkins, K.S.M.,Counsell, C.(2003).Systematic review of incidence studies of Parkinson's disease.Move. Dis.,18,19-31.
  106. Usuki, F.,Yasutake, A.,Umehara, F.,Tokunaga, H.,Matsumoto, M.,Eto, K.,Ishiura, S.,Higuchi, I.(2001).In vivo protection of a watersoluble derivative of vitamin E, Trolox, against methylmercuryintoxication in the rat.Neurosci. Lett.,304,199-203.
  107. Voorhees, C.V.(1986).Handbook of Behavioral Teratology.New York:Plenum Press.
  108. Wagner, G.C.,Carelli, R.M.,Jarvis, M.F.(1986).Ascorbic acid reduces the dopamine depletion induced by METH and the 1-methyl-4-phenyl pyridinium ion..Neuropharmacology,25,559-561.
  109. Wagner, G.C.,Jarvis, M.F.,Carelli, R.M.(1985).Ascorbic acid reduces the dopamine depletion induced by MPTP.Neuropharmacology,24,1261-1262.
  110. Wagner, G.C.,Walsh, S.L.(1991).Evaluation of the effects of inhibition of monoamine oxidase and senescence on methamphetamineinduced neuronal damage.Int. J. Dev. Neurosci.,9,171-174.
  111. Wagner, G.C,Reuhl, K.R.,Cheh, M.,McRae, P.,Halladay, A.K.(2006).A new neurobehavioral model of autism in mice: Pre- and Postnatal exposure to sodium valproate.J. Autism Dev. Dis.,36,779-793.
  112. Wakefield, A.J.,Murch, S.H.,Anthony, A.,Linnell, J.,Casson, D.M.,Maiik, M.,Berelowitz, M.,Dhillon, A.P.,Thompson, M.A.,Harvey, P.,Valentine, A.,Davies, S.E.,Walker-Smith, J.A.(1998).Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.Lancet,351,637-641.
  113. Wassink, T.H.,Hazlet, H.C.,Epping, E.A.,Ardnt, S.,Dager, S.R.,Schellenberg, G.D.,Dawson, G.,Piven, J.(2007).Cerebral cortical gray matter overgrowth and functional variation of the serotonin transporter gene in autism.Arch. Gen. Psychiatry,64,709-717.
  114. West, A.B.,Moore, D.J.,Biskup, S.,Bugayenko, A.,Smith, W.W.,Ross, C.A.,Dawson, V.L.,Dawson, T.M.(2005).Parkinson's diseaseassociated mutations in leucine-rich repeat kinase 2 augment kinase activity.Proc. Natl. Acad. Sci.,102,16842-16847.
  115. Whittaker-Azmitia, P.M.(2005).Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism?.Int. J. Dev. Neurosci.,23,75-83.
  116. Williams, G.,King, J.,Cunningham, M.,Stephan, M.,Kerr, B.,Hersh, J.H.(2001).Fetal valproate syndrome and autism: additional evidence of an association.Dev. Med. Child Neurol.,43,202-206.
  117. Williams, T.A.,Mars, A.E.,Buyske, S.G.,Stenroos, E.S.,Wang, R.,Factura-Santiago, M.F.,Lambert, G.H.,Johnson, W.G.(2007).Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype.Arch. Pediatr. Adolesc. Med.,161,356-361.
  118. Windham, G.C.,Zhang, L.,Gunier, R.,Croen, L.A.,Grether, J.K.(2006).Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area.Environ. Health Perspect.,114,1438-1444.
  119. Yamauchi, N.,Watanabe, N.,Kuriyama, H.,Neda, H.,Maeda, M.,Himeno, T.,Tsuji, Y.,Niitsu, Y.(1990).Suppressive effects of intracellular glutathione on hydroxyl radical production induced by tumor necrosis factor.Int. J. Cancer,46,884-888.
  120. Yee, S.,Choi, B.H.(1996).Oxidative stress in neurotoxic effects of methylmercury poisoning.Neurotoxicology,17,17-26.
  121. Yochum, C.L.,Dowling, P.,Reuhl, K.R.,Wagner, G.C.,Ming, X.(2008).VPA-induced apoptosis and behavioral deficits in neonatal mice.Brain Res.,1203,126-132.
  122. Zoroglu, S.S.,Armutcu, F.,Ozen, S.,Gurel, A.,Sivasli, E.,Yetkin, O.,Meram, I.(2004).Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism.Eur. Arch. Psychi. Clin. Neurosci.,254,143-147.
  123. Zuckerman, L.,Weiner, I.(2005).Maternal immune activation leads to behavioral and pharmacological changes in adult offspring.J. Psychi. Res.,39,311-323.