Exposure to organophosphates reduces the expression of neurotrophic factors in neonatal rat brain regions: Similarities and differences in the effects of chlorpyrifos and diazinon on the fibroblast growth factor superfamily

Environmental Health Perspectives

Volumn 115, Issue 6, 2007, Pages 909-916

  Slotkin, Theodore A ^a   Seidler, Frederic J ^a   Fumagalli, Fabio ^b  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

Brain development; Chlorpyrifos; Diazinon; Fibroblast growth factor; Fibroblast growth factor receptors; Microarrays; Neurotoxicity; Organophosphate insecticides

Indexed keywords

CHLORPYRIFOS; CHOLINESTERASE; DIMPYLATE; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 1; FIBROBLAST GROWTH FACTOR 18; FIBROBLAST GROWTH FACTOR 2; FIBROBLAST GROWTH FACTOR 23; FIBROBLAST GROWTH FACTOR 3; FIBROBLAST GROWTH FACTOR 9; FIBROBLAST GROWTH FACTOR RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 3; FIBROBLAST GROWTH FACTOR RECEPTOR 4; MESSENGER RNA; NEUROTROPHIC FACTOR; ORGANOPHOSPHATE PESTICIDE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BRAIN REGION; BRAIN STEM; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; ENZYME INHIBITION; FOREBRAIN; INHIBITION KINETICS; MICROARRAY ANALYSIS; NERVE CELL DIFFERENTIATION; NERVOUS SYSTEM DEVELOPMENT; NEUROTOXICITY; NEWBORN; NONHUMAN; NUCLEOTIDE SEQUENCE; PERINATAL PERIOD; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; RAT;

ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; BRAIN; CHLORPYRIFOS; DIAZINON; DOSE-RESPONSE RELATIONSHIP, DRUG; FIBROBLAST GROWTH FACTORS; GENE EXPRESSION REGULATION; INSECTICIDES; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; RATS;

RATTUS;

EID: 34250163568     PISSN: 00916765     EISSN: 15529924     Source Type: Journal    
DOI: 10.1289/ehp.9901     Document Type: Article

References (112)

1. Abdel-Rahman A, Dechkovskaia AM, Mehta-Simmons H, Guan S, Khan WA, Abou-Donia MB. 2003. Increased expression of glial fibrillary acidic protein in cerebellum and hippocampus: differential effects on neonatal brain regional acetylcholinesterase following maternal exposure to combined chlorpyrifos and nicotine. J Toxicol Environ Health A 66:2047-2066.
2. Aldridge JE, Levin ED, Seidler FJ, Slotkin TA. 2005a. Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 113:527-531.
3. Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. 2005b. Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure. Environ Health Perspect 113:1027-1031.
4. Aldridge JE, Seidler FJ, Slotkin TA. 2004. Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling. Environ Health Perspect 112:148-155.
5. Axelrad JC, Howard CV, McLean WG. 2003. The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon. Toxicology 185:67-78.
6. Barone S, Das KP, Lassiter TL, White LD. 2000. Vulnerable processes of nervous system development: a review of markers and methods. Neurotoxicology 21:15-36.
7. Belluardo N, Mudo G, Blum M, Itoh N, Agnati L, Fuxe K. 2004. Nicotine-induced FGF-2 mRNA in rat brain is preserved during aging. Neurobiol Aging 25:1333-1342.
8. Betancourt AM, Burgess SC, Carr RL. 2006. Effect of developmental exposure to chlorpyrifos on the expression of neurotrophin growth factors and cell-specific markers in neonatal rat brain. Toxicol Sci 92:500-506.
9. Betancourt AM, Carr RL. 2004. The effect of chlorpyrifos and chlorpyrifos-oxon on brain cholinesterase, muscarinic receptor binding, and neurotrophin levels in rats following early postnatal exposure. Toxicol Sci 77:63-71.
10. Blak AA, Naserke T, Weisenhorn DMV, Prakash N, Partanen J, Wurst W. 2005. Expression of Fgf receptors 1, 2, and 3 in the developing mid-and hindbrain of the mouse. Dev Dynamics 233:1023-1030.
11. Bloomquist JR, Barlow RL, Gillette JS, Li W, Kirby ML. 2002. Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways. Neurotoxicology 23:537-544.
12. Braak H, Muller CM, Rub U, Ackermann H, Bratzke H, de Vos RA, et al. 2006. Pathology associated with sporadic Parkinson's disease - where does it end? J Neural Transmission Suppl 70:89-97.
13. Brimijoin S, Koenigsberger C. 1999. Cholinesterases in neural development: new findings and toxicologic implications. Environ Health Perspect 107(suppl 1):59-64.
14. Campbell CG, Seidler FJ, Slotkin TA. 1997. Chlorpyrifos interferes with cell development in rat brain regions. Brain Res Bull 43:179-189.
15. Carr RL, Chambers HW, Guarisco JA, Richardson JR, Tang J, Chambers JE. 2001. Effects of repeated oral postnatal exposure to chlorpyrifos an open-field behavior in juvenile rats. Toxicol Sci 59:260-267.
16. Casida JE, Quistad GB. 2004. Organophosphate toxicology: safety aspects of nonacetylcholinesterase secondary targets. Chem Res Toxicol 17:983-998.
17. Chakraborti TK, Farrar JD, Pope CN. 1993. Comparative neuro-chemical and neurobehavioral effects of repeated chlorpyrifos exposures in young and adult rats. Pharmacol Biochem Behav 46:210-224.
18. Clegg DJ, van Gemert M. 1999. Determination of the reference dose for chlorpyrifos: proceedings of an expert panel. J Toxicol Environ Health 2:211-255.
19. Colborn T. 2006. A case for revisiting the safety of pesticides: a closer look at neurodevelopment. Environ Health Perspect 114:10-17,
20. Cool SM, Sayer RE, van Heumen WR, Pickles JO, Nurcombe V. 2002. Temporal and spatial expression of fibroblast growth factor receptor 4 isoforms in murine tissues. Histochem J 34:291-297.
21. Cory-Slechta DA, Thiruchelvam M, Barlow BK, Richfield EK. 2005. Developmental pesticide models of the Parkinson Disease phenotype. Environ Health Perspect 113:1263-1270.
22. Cost, LG. 2006. Current issues in organophosphate toxicology. Clin Chim Acta 366:1-13.
23. Dam K, Garcia SJ, Seidler FJ, Slotkin TA. 1999. Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways. Dev Brain Res 116:9-20.
24. Dam K, Seidler FJ, Slotkin TA. 2000. Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity. Dev Brain Res 121:179-187.
25. Damier P, Hirsch EC, Agid Y, Graybiel AM. 1999. The substantia nigra of the human brain. I. Nigrosomes and the nigral matrix, a compartmental organization based on calbindin D(28K) immunohistochemistry. Brain Dev 122:1421-1436.
26. Damodaran TV, Greenfield ST, Patel AG, Dressman HK, Lin SK, Abou-Donia MB. 2006a. Toxicogenomic studies of the rat brain at an early time point following acute sarin exposure. Neurochem Res 31:367-381.
27. Damodaran TV, Patel AG, Greenfield ST, Dressman HK, Lin SM, Abou-Donia MB. 2006b. Gene expression profiles of the rat brain both immediately and 3 months following acute sarin exposure. Biochem Pharmacol 71:497-520.
28. Das KP, Barone S. 1999. Neuronal differentiation in PC12 cells is inhibited by chlorpyrifos and its metabolites: is acetyl-cholinesterase inhibition the site of action? Toxicol Appl Pharmacol 160:217-230.
29. De Peyster A, Willis WO, Molgaard CA, MacKendrick TM, Walker C. 1993. Cholinesterase and self-reported pesticide exposure among pregnant women. Arch Environ Health 48:348-352.
30. Dobbing J, Sands J. 1979. Comparative aspects of the brain growth spurt. Early Human Dev 3:79-83.
31. Dono R. 2003. Fibroblast growth factors as regulators of central nervous system development and function. Am J Physiol 284:R867-R881.
32. Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, et al. 2007. Organophosphate pesticide exposure and neuro-development in young Mexican-American children. Environ Health Perspect 115:792-798; doi:10.1289/ehp.9828 [Online 4 January 2007].
33. Fumagalli F, Bedogni F, Slotkin TA, Racagni G, Riva MA. 2005. Prenatal stress elicits regionally-selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress. Neurobiol Dis 20:731-737.
34. Gage FH, Ray J, Fisher L. 1995. Isolation, characterization, and use of stem cells from the CNS. Annu Rev Neurosci 18:159-192.
35. GenBank. 2007. GenBank Overview. Available: http.//www.ncbi.nlm.nih.gov/ Genbank/index.html [accessed 25 April 2007].
36. Gomez-Pinilla, Lee JW, Cotman CW. 1994. Distribution of basic fibroblast growth factor in the developing rat brain. Neuroscience 61:911-923.
37. Gupta RC. 2004. Brain regional heterogeneity and toxicological mechanisms of organophosphates and carbamates. Toxicol Mech Meth 14:103-143.
38. Gurunathan S, Robson M, Freeman N, Buckley B, Roy A, Meyer R, et al. 1998. Accumulation of chlorpyrifos on residential surfaces and toys accessible to children. Environ Health Perspect 106:9-16,
39. Hart KC, Robertson SC, Kanemitsu MY, Meyer AN, Tynan JA, Donoghue DJ. 2000. Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene 19:3309-3320.
40. Hirsch EC. 1994. Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. Mol Neurobiol 9:135-142.
41. Howard AS, Bucelli R, Jett DA, Bruun D, Yang DR. 2005. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures. Toxicol Appl Pharmacol 207:112-124.
42. Icenogle LM, Christopher C, Blackwelder WP, Caldwell DP, Qiao D, Seidler FJ, et al. 2004. Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation. Neurotoxicol Teratol 26:95-101.
43. Jameson RR, Seidler FJ, Qiao D, Slotkin TA. 2006. Chlorpyrifos effects phenotypic outcomes in a model of mammalian neurodevelopment: critical stages targeting differentiation in PC12 cells. Environ Health Perspect 114:667-672.
44. Jameson RR, Seidler FJ, Slotkin TA. 2007. Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates: chlorpyrifos, chlorpyrifos oxon and diazinon. Environ Health Perspect 115:65-70.
45. Jett DA, Navoa RV. 2000. In vitro and in vivo effects of chlorpyrifos on glutathione peroxidase and catalase in developing rat brain. Neurotoxicology 21:141-145.
46. Johe KK, Hazel TG, Muller T, Dugich-Djordjevic MM, McKay RDG. 1996. Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev 10:3129-3140.
47. Kamel F, Hoppin JA. 2004. Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect 112:950-958.
48. Karen DJ, Li W, Harp PR, Gillette JS, Bloomquist JR. 2001. Striatal dopaminergic pathways as a target for the insecticides permethrin and chlorpyrifos. Neurotoxicology 22:811-817.
49. Kempermann G, Kuhn HG, Gage FH. 1997. More hippocampal neurons in adult mice living in an enriched environment. Nat Biotechnol 386:493-495.
50. Krieglstein K, Reuss B, Maysinger D, Unsicker K. 1998. Transforming growth factor-beta mediates the neurotrophic effect of fibroblast growth factor-2 on midbrain dopaminergic neurons. Eur J Neurosci 10:2746-2750.
51. Landrigan PJ. 2001. Pesticides and polychlorinated biphenyls (PCBs): an analysis of the evidence that they impair children's neurobehavioral development. Mol Genet Metab 73:11-17.
52. Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D. 2005. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 113:1230-1233.
53. Lassiter TL, Padilla S, Mortensen SR, Chanda SM, Moser VC, Barone S. 1998. Gestational exposure to chlorpyrifos: apparent protection of the fetus? Toxicol Appl Pharmacol 152:56-65.
54. Lazarini CA, Lima RY, Guedes AP, Bernardi MM. 2004. Prenatal exposure to dichlorvos: physical and behavioral effects on rat offspring. Neurotoxicol Teratol 26:607-614.
55. Levin ED, Addy N, Baruah A, Elias A, Christopher NC, Seidler FJ, et al. 2002. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations. Neurotoxicol Teratol 24:733-741.
56. Levin ED, Addy N, Christopher NC, Seidler FJ, Slotkin TA. 2001. Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Dev Brain Res 130:83-89.
57. Limke TL, Cai J, Miura T, Rao MS, Mattson MP. 2003. Distinguishing features of progenitor cells in the late embryonic and adult hippocampus. Dev Neurosci 25:257-272.
58. Lou J-Y, Laezza F, Gerber BR, Xiao M, Yamada KA, Hartmann H, et al. 2005. Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels. J Physiol 569:179-193.
59. Luo Y, Cai J, Liu Y, Xue H, Chrest FJ, Wersto RP, et al. 2002. Microarray analysis of selected genes in neural stem and progenitor cells. J Neurochem 83:1481-1497.
60. Mense SM, Sengupte A, Lan C, Zhou M, Bentsman G, Volsky DJ, et al. 2006. The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci 93:125-135.
61. Mileson BE, Chambers JE, Chen WL, Dettbarn W, Ehrich M, Eldefrawi AT, et al. 1998. Common mechanism of toxicity: a case study of organophosphorus pesticides. Toxicol Sci 41:8-20.
62. Miyake A, Itoh N. 1996. Rat fibroblast growth factor receptor-4 mRNA in the brain is preferentially expressed in cholinergic neurons in the medial habenular nucleus. Neurosci Lett 203:101-104.
63. Monfils MH, Driscoll I, Melvin NR, Kolb B. 2006. Differential expression of basic fibroblast growth factor-2 in the developing rat brain. Neuroscience 141:213-221.
64. Monfils M-H, Driscoll I, Vandenberg PM, Thomas NJ, Danko D, Kleim JA, et al. 2005. Basic fibroblast growth factor stimulates functional recovery after neonatal lesions of motor cortex in rats. Neuroscience 134:1-8.
65. Murase S, McKay RD. 2006. A specific survival response in dopamine neurons at most risk in Parkinson's disease. J Neurosci 26:9750-9760.
66. Ohmachi S, Watanabe Y, Mikami T, Kusu N, Ibi T, Akaike A, et al. 2000. FGFR-20, a novel neurotrophic factor, preferentially expressed in the substantia nigra pars compacta of rat brain. Biochem Biophys Res Comm 277:355-360.
67. Olanow CW, Arendash GW. 1994. Metals and free radicals in neurodegeneration. Curr Opin Neurol 7:548-558.
68. Ostrea EM, Morales V, Ngoumgna E, Prescilla R, Tan E, Hernandez E, et al. 2002. Prevalence of fetal exposure to environmental toxins as determined by meconium analysis. Neurotoxicology 23:329-339.
69. Otto D, Unsicker K. 1990. Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 10:1912-1921.
70. Pope C, diLorenzo K, Ehrich M. 1995. Possible involvement of a neurotrophic factor during the early stages of organophosphate-induced delayed nourotoxicity. Toxical Lett 75:111-117.
71. Pope CN. 1999. Organophosphorus pesticides: do they all have the same mechanism of toxicity? J Toxicol Environ Health 2:161-181.
72. Pung T, Klein B, Blodgett D, Jortner B, Ehrich M. 2006. Examination of concurrent exposure to repeated stress and chlorpyrifos on cholinergic, glutamatergic, and monoamine neurotransmitter systems in rat forebrain regions. Intl J Toxicol 25:65-80.
73. Qiao D, Seidler FJ, Abreu-Villaça Y, Tate CA, Cousins MM, Slotkin TA. 2004. Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood. Dev Brain Res 148:43-52.
74. Qiao D, Seidler FJ, Slotkin TA. 2001. Developmental neurotoxicity of chlorpyrifos modeled in vitro: comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells. Environ Health Perspect 109:909-913.
75. Qiao D, Seidler FJ, Tate CA, Cousins MM, Slotkin TA. 2003. Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood. Environ Health Perspect 111:536-544.
76. Quik M, Di Monte DA. 2001. Nicotine administration reduces striatal MPP+ levels in mice, Brain Res 917:219-224.
77. Rauh VA, Garfinkel R, Perera R, Andrews H, Hoepner L, Barr D, et al. 2006. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics 118:1845-1859.
78. Ray J, Peterson DA, Schinstine M, Gage FH. 1993. Proliferation, differentiation, and long-term culture of primary hippocampal neurons. Proc Natl Aced Sci USA 90:3602-3606.
79. Ricceri L, Venerosi A, Capone F, Comete MF, Lorenzini P, Fortuna S, et al. 2006. Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice. Toxicol Sci 93:105-113.
80. Rice D, Barone S. 2000. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108(suppl 3):511-533.
81. Richardson JR, Chambers JE. 2004. Neurochemical effects of repeated gestational exposure to chlorpyrifos in developing rats. Toxicol Sci 77:83-90.
82. Richardson JR, Chambers JE. 2005. Effects of repeated oral postnatal exposure to chlorpyrifos on cholinergic neuro-chemistry in developing rats. Toxicol Sci 84:352-359.
83. Rodier PM. 1988. Structural-functional relationships in experimentally induced brain damage. Prog Brain Res 73:335-348.
84. Roy TS, Sharma V, Seidler FJ, Slotkin TA. 2005. Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats. Dev Brain Res 155:71-80.
85. Shults CW, Ray J, Tsuboi K, Gage FH. 2000. Fibroblast growth factor-2-producing fibroblasts protect the nigrostriatal dopaminergic system from 6-hydroxydopamine. Brain Res 883:192-204.
86. Slotkin TA. 1999. Developmental cholinotoxicants: nicotine and chlorpyrifos. Environ Health Perspect 107(suppl 1):71-80.
87. Slotkin TA. 2004. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol 198:132-151.
88. Slotkin TA. 2005. Developmental nourotoxicity of organophosphates: a case study of chlorpyrifos. In: Toxicity of Organophosphate and Carbamate Pesticides (Gupta RC, ed). San Diego:Elsevier Academic Press, 293-314.
89. Slotkin TA, Cousins MM, Tate CA, Seidler FJ. 2001. Persistent cholinergic presynaptic deficits after neonatal chlorpyrifos exposure. Brain Res 902:229-243.
90. Slotkin TA, Levin ED, Seidler FJ. 2006a. Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity. Environ Health Perspect 114:746-751.
91. Slotkin TA, MacKillop EA, Ryde IT, Tate CA, Seidler FJ. 2007. Screening for developmental neurotoxicity using PC12 cells: comparisons of organophosphates with a carbamate, an organochlorine, and divalent nickel. Environ Health Perspect 115:93-101.
92. Slotkin TA, Oliver CA, Seidler FJ. 2005. Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination. Dev Brain Res 157:172-180.
93. Slotkin TA, Seidler FJ. 2007. Prenatal chlorpyrifos exposure elicits presynaptic serotonergic and dopaminergic hyper-activity at adolescence: critical periods for regional and sex-selective effects. Reprod Toxicol 23:421-427.
94. Slatkin TA, Tate CA, Cousins MM, Seidler FJ. 2002. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Dev Brain Res 133:163-173.
95. Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. 2006b. Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition. Environ Health Perspect 114:1542-1546.
96. Song Y, Seidler FJ, Saleh JL, Zhang J, Padilla S, Slotkin TA. 1997. Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade. Toxicol Appl Pharmacol 145:158-174.
97. Song X, Violin JD, Seidler FJ, Slotkin TA. 1998. Modeling the developmental neurotoxicity of chlorpyrifos in vitro: macromolecule synthesis in PC12 cells. Toxicol Appl Pharmacol 151:162-191.
98. Takagi Y, Takahashi J, Saki H, Morizane A, Hayashi T, Kishi Y, et al. 2005. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 115:102-109.
99. Tao Y, Black IB, DiCicco-Bloom E. 1997. In vivo nourogenesis is inhibited by neutralizing antibodies to basic fibroblast growth factor. J Neurobiol 33:289-296.
100. Terry AV, Stone JD, Buccafusco JJ, Sickles DW, Sood A, Prendergast MA. 2003. Repeated exposures to subthreshold doses of chlorpyrifos in rats: hippocampal damage, impaired axonal transport, and deficits in spatial learning. J Pharmacol Exp Ther 305:375-384.
101. Tooyama I, Kawamata T, Walker D, Yamada T, Hanai K, Kimura H, et al. 1993. Loss of basic fibroblast growth factor in substantia nigro neurons in Parkinson's disease. Neurology 43372-376.
102. Umemori H, Linhoff MW, Ornitz DM, Sanes JR. 2004. FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain. Cell 118:257-270.
103. U.S. Environmental Protection Agency. 2006. Opportunities to Improve Data Quality and Children's Health Through the Food Quality Protection Act. Report no. 2006-P-00009. Available: http://www.epa.gov/oig/reports/ 2006/20060110-2006-P-00009.pdf [accessed 7 July 2006].
104. van der Walt JM, Noureddine MA, Kittappa R, Hauser MA, Scott WK, McKay R, et al. 2004. Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. Am J Human Genet 74:1121-1127.
105. Wang Q, Bardgett ME, Wong M, Wozniak DF, Lou J, McNeil BD, et al. 2002. Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14. Neuron 35:25-38.
106. Wang Q, McEwen DG, Ornitz DM. 2000. Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14. Mach Dev 90:283-287.
107. Weiss B, Amler S, Amler RW. 2004. Pesticides. Pediatrics 113:1030-1036.
108. Whitney KD, Seidler FJ, Slotkin TA. 1995. Developmental neurotoxicity of chlorpyrifos: cellular mechanisms. Toxicol Appl Pharmacol 134:53-62.
109. Wright TJ, Ladher R, McWhirter J, Murre C, Schoenwolf GC, Mansour SL. 2004. Mouse FGF15 is the ortholog of human and chick FGF19, but is not uniquely required for otic induction. Dev Biol 269:264-275.
110. Yamada T, McGeer PL, Baimbridge KG, McGeer EG. 1990. Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res 526:303-307.
111. Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, et al. 2001. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci USA 98:5874-5879.
112. Young JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, et al. 2005. Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology 26:199-209.