Superfund Research Program
Developmental Neurotoxicity of Superfund Pesticides: Biomarkers and Mechanisms
Project Leader: Theodore A. Slotkin (Duke University Medical Center)
Grant Number: P42ES010356
Funding Period: 2000-2011
Project-Specific Links
Publications
2011
- Powers CM, Levin ED, Seidler FJ, Slotkin TA. 2011. Silver exposure in developing zebrafish produces persistent synaptic and behavioral changes. Neurotoxicol Teratol 33:329-332. doi:10.1016/j.ntt.2010.10.006 PMID:21035540 PMCID:PMC3071894
- Slotkin TA. 2011. Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity?. Reprod Toxicol 31:297-301. doi:10.1016/j.reprotox.2010.07.012 PMID:20850519 PMCID:PMC3025269
2010
- Powers CM, Wrench N, Ryde IT, Smith AA, Seidler FJ, Slotkin TA. 2010. Silver impairs neurodevelopment: studies in PC12 cells. Environ Health Perspect 118(1):73-79. doi:10.1289/ehp.0901149 PMID:20056586 PMCID:PMC2831971
- Powers CM, Yen J, Linney EA, Seidler FJ, Slotkin TA. 2010. Silver exposure in developing zebrafish (Danio rerio): persistent effects on larval behavior and survival. Neurotoxicol Teratol 32(3):391-397. doi:10.1016/j.ntt.2010.01.009 PMID:20116428 PMCID:PMC2854181
2009
- Slotkin TA, Seidler FJ. 2009. Protein kinase C is a target for diverse developmental neurotoxicants: transcriptional responses to chlorpyrifos, diazinon, dieldrin and divalent nickel in PC12 cells. Brain Res 1263:23-32. doi:10.1016/j.brainres.2009.01.049 PMID:19368821 PMCID:PMC2670938
- Slotkin TA, Wrench N, Ryde IT, Lassiter TL, Levin ED, Seidler FJ. 2009. Neonatal parathion exposure disrupts serotonin and dopamine synaptic function in rat brain regions: modulation by a high-fat diet in adulthood. Neurotoxicol Teratol 31(6):390-399. doi:10.1016/j.ntt.2009.07.003 PMID:19616088 PMCID:PMC2761992
2008
- Roegge CS, Timofeeva OA, Seidler FJ, Slotkin TA, Levin ED. 2008. Developmental diazinon neurotoxicity in rats: later effects on emotional response. Brain Res Bull 75:168-172. PMID:18158111
- Slotkin TA, Bodwell BE, Levin ED, Seidler FJ. 2008. Neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems. Environ Health Perspect 116(3):340-348. doi:10.1289/ehp.11005 PMID:18335101 PMCID:PMC2265026
- Slotkin TA, Ryde IT, Levin ED, Seidler FJ. 2008. Developmental neurotoxicity of low dose diazinon exposure of neonatal rats: effects on serotonin systems in adolescence and adulthood. Brain Res Bull 75(5):640-647. doi:10.1016/j.brainresbull.2007.10.008 PMID:18355640 PMCID:PMC2322865
- Slotkin TA, Seidler FJ. 2008. Developmental neurotoxicants target neurodifferentiation into the serotonin phenotype: Chlorpyrifos, diazinon, dieldrin and divalent nickel. Toxicol Appl Pharmacol 233(2):211-219. doi:10.1016/j.taap.2008.08.020 PMID:18835401 PMCID:PMC2645545
- Slotkin TA, Seidler FJ, Fumagalli F. 2008. Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro. Brain Res Bull 76(4):424-438. doi:10.1016/j.brainresbull.2008.01.001 PMID:18502319 PMCID:PMC2430428
- Slotkin TA, Seidler FJ, Ryde IT, Yanai J. 2008. Developmental neurotoxicity of chlorpyrifos in an avian model: effects on acetylcholine and serotonin pathways. Neurotoxicol Teratol PMID:18436430
- Timofeeva OA, Roegge CS, Seidler FJ, Slotkin TA, Levin ED. 2008. Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide, diazinon. Neurotoxicol Teratol 30(1):38-45. doi:10.1016/j.ntt.2007.10.002 PMID:18096363 PMCID:PMC2262840
2007
- Buznikov GA, Nikitina LA, Rakic LM, Milosevic I, Bezuglov VV, Lauder JM, Slotkin TA. 2007. The sea urchin embryo, an invertebrate model for mammalian developmental neurotoxicity, reveals multiple neurotransmitter mechanisms for effects of chlorpyrifos: therapeutic interventions and a comparison with the monoamine depleter, reserpine. Brain Res Bull 74(4):221-231. PMID:17720543
- 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(1):65-70. PMID:17366821 PMCID:PMC1797835
- Slotkin TA, MacKillop EA, Ryde IT, Seidler FJ. 2007. Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells. Environ Health Perspect 115:1306-1313. PMID:17805420
- 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(1):93-101. PMID:17366826 PMCID:PMC1797840
- Slotkin TA, Seidler FJ. 2007. Comparative developmental neurotoxicity of organophosphates in vivo: transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res 72:232-274. PMID:17452286
- Slotkin TA, Seidler FJ. 2007. Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats. Brain Res Bull 73(4-6):301-9. PMID:17562396
- Slotkin TA, Seidler FJ. 2007. Prenatal chlorpyrifos exposure elicits presynaptic serotonergic and dopaminergic hyperactivity at adolescence: critical periods for regional and sex-selective effects. Reprod Toxicol 23(3):421-7. PMID:17267174
- Slotkin TA, Seidler FJ, Fumagalli F. 2007. 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. Environ Health Perspect 115(6):909-16. PMID:17589599
2006
- Jameson RR, Seidler FJ, Qiao D, Slotkin TA. 2006. Adverse neurodevelopmental effects of dexamethasone modeled in PC12 Cells: identifying the critical stages and concentration thresholds for the targeting of cell acquisition, differentiation and viability. Neuropsychopharmacology 31(8):1647-1658. PMID:16319912
- Jameson RR, Seidler FJ, Qiao D, Slotkin TA. 2006. Chlorpyrifos affects phenotypic outcomes in a model of mammalian neurodevelopment: critical stages targeting differentiation in PC12 cells. Environ Health Perspect 114:667-672. PMID:16675418
- Slotkin TA, Seidler FJ. 2006. Anomalous regulation of B-adrenoceptor signaling in brain regions of the newborn rat. Brain Res 1077(1):54-58.
2005
- Aldridge JE, Levin ED, Seidler FJ, Slotkin TA. 2005. 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(5):527-531. PMID:15866758
- Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. 2005. Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure. Environ Health Perspect 113(8):1027-1031. PMID:16079074 PMCID:PMC1280344
- Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. 2005. Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions. Toxicol Appl Pharmacol 203(2):132-144. PMID:15710174
- Garcia SJ, Seidler FJ, Slotkin TA. 2005. Developmental neurotoxicity of chlorpyrifos: targeting glial cells. Environ Toxicol Pharmacol 19(3):455-461. doi:10.1016/j.etap.2004.12.007 PMID:21783512
- Meyer A, Seidler FJ, Aldridge JE, Slotkin TA. 2005. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos. Toxicol Appl Pharmacol 203(2):154-166. PMID:15710176
- Qiao D, Seidler FJ, Slotkin TA. 2005. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos. Toxicol Appl Pharmacol 206(1):17-26. PMID:15963341
- 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. Brain Res Dev Brain Res 155(1):71-80. doi:10.1016/j.devbrainres.2004.12.004 PMID:15763277
- Slotkin TA. 2005. Developmental Neurotoxicity of Organophosphates: A Case Study of Chlorpyrifos. Chapter 21 in: Toxicity of Organophosphate and Carbamate Compounds. (Gupta RC, ed). Elsevier Academic Press, San Diego, CA. pp.293-314.
- Slotkin TA, Brown KK, Seidler FJ. 2005. Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood. Environ Health Perspect 113(10):1291-1294. PMID:16203236 PMCID:PMC1281268
- 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. Brain Res Dev Brain Res 157(2):172-180. PMID:15963356
- Slotkin TA, Seidler FJ. 2005. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent. Brain Res Dev Brain Res 158(1-2):115-119. doi:10.1016/j.devbrainres.2005.06.008 PMID:16024092
- Slotkin TA, Tate CA, Cousins MM, Seidler FJ. 2005. Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination. Brain Res Dev Brain Res 160(2):219-230. PMID:16256208
2004
- 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(2):148-155. PMID:14754568
- Icenogle LM, Christopher NC, Blackwelder WP, Caldwell DP, Qiao D, Seidler FJ, Slotkin TA, Levin ED. 2004. Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation. Neurotoxicol Teratol 26(1):95-101. PMID:15001218
- Izrael M, Van der Zee EA, Slotkin TA, Yanai J. 2004. Cholinergic synaptic signaling mechanisms underlying behavioral teratogenicity: effects of nicotine, chlorpyrifos, and heroin converge on protein kinase C translocation in the intermedial part of the hyperstriatum ventrale and on imprinting behavior in an avian model. J Neurosci Res 78(4):499-507. doi:10.1002/jnr.20287 PMID:15470723
- Meyer A, Seidler FJ, Aldridge JE, Tate CA, Cousins MM, Slotkin TA. 2004. Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure. Environ Health Perspect 112(3):295-301. PMID:14998743
- Meyer A, Seidler FJ, Slotkin TA. 2004. Developmental effects of chlorpyrifos extend beyond neurotoxicity: critical periods for immediate and delayed-onset effects on cardiac and hepatic cell signaling. Environ Health Perspect 112(2):170-178. PMID:14754571
- Qiao D, Seidler FJ, Abreu-Villaca 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. Brain Res Dev Brain Res 148(1):43-52. PMID:14757517
- Rhodes MC, Seidler FJ, Qiao D, Tate CA, Cousins MM, Slotkin TA. 2004. Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats. Toxicol Appl Pharmacol 195(2):203-217. doi:10.1016/j.taap.2003.11.008 PMID:14998686
- Roy TS, Seidler FJ, Slotkin TA. 2004. Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain: regionally selective alterations in neurons and glia. Brain Res Dev Brain Res 148(2):197-206. doi:10.1016/j.devbrainres.2003.12.004 PMID:14766197
- Slotkin TA. 2004. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol 198(2):132-151. PMID:15236950
- Slotkin TA. 2004. Guidelines for developmental neurotoxicity and their impact on organophosphate pesticides: a personal view from an academic perspective. Neurotoxicology 25(4):631-640. PMID:15183016
- Slotkin TA, Southard MC, Adam SJ, Cousins MM, Seidler FJ. 2004. Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos. Brain Res Bull 64(3):227-235. doi:10.1016/j.brainresbull.2004.07.005 PMID:15464859
2003
- Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. 2003. Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods. Environ Health Perspect 111(14):1736-1743. PMID:14594624
- Buznikov GA, Slotkin TA, Lauder JM. 2003. Sea urchin embryos and larvae as biosensors for neurotoxins. In: Current Protocals in Toxicology. John Wiley & Sons, NY. pp.1.6.1-1.6.24.
- Dam K, Seidler FJ, Slotkin TA. 2003. Transcriptional biomarkers distinguish between vunerable periods for developmental neurotoxicity of chlorpyrifos: implications for toxicogenomics. Brain Res Bull 59(4):261-265. PMID:12464398
- Garcia SJ, Seidler FJ, Slotkin TA. 2003. Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities. Environ Health Perspect 111(3):297-303. PMID:12611658 PMCID:PMC1241386
- Meyer A, Seidler FJ, Cousins MM, Slotkin TA. 2003. Developmental neurotoxicity elicited by gestational exposure to chlorpyrifos: when is adenylyl cyclase a target?. Environ Health Perspect 111(16):1871-1876. PMID:14644659 PMCID:PMC1241759
- Nikitina LA, Buznikov GA, Lauder JM, Seidler FJ, Slotkin TA. 2003. The sea urchin embryo as a model for mammalian developmental neurotoxicity: ontogenesis of the high-affinity choline transporter and its role in cholinergic trophic activity. Environ Health Perspect 111(14):536-544. PMID:14594623
- Qiao D, Seidler FJ, Violin JD, Slotkin TA. 2003. Nicotine is a developmental neurotoxicant and neuroprotectant: stage-selective inhibition of DNA synthesis coincident with shielding from effects of chlorpyrifos. Brain Res Dev Brain Res 147(1-2):183-190. PMID:14741763
- 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(4):536-544. PMID:12676612 PMCID:PMC1241441
2002
- Garcia SJ, Seidler FJ, Slotkin TA. 2002. Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein. Brain Res Dev Brain Res 133(2):151-161. PMID:11882345
- Levin ED, Addy N, Baruah A, Elias A, Christopher NC, Seidler FJ, Slotkin TA. 2002. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations. Neurotoxicol Teratol 24(6):733-741. PMID:12460655
- Seidler FJ, Padilla S, Slotkin TA, Qiao D. 2002. Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period?. Environ Health Perspect 110(11):1097-1103. PMID:12417480 PMCID:PMC1241065
- Slotkin TA, Tate CA, Cousins MM, Seidler FJ. 2002. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Brain Res Dev Brain Res 133(2):163-173. PMID:11882346
- Yanai J, Vatury O, Slotkin TA. 2002. Cell signaling as a target and underlying mechanism for neurobehavioral teratogenesis. Ann N Y Acad Sci 965:473-478. PMID:12105122
2001
- Arthur D, Levin ED. 2001. Spatial and non-spatial visual discrimination learning in zebrafish (Danio rerio). Anim Cogn 4:125-131.
- Buznikov GA, Bezuglov VV, Nikitina LA, Slotkin TA, Lauder JM. 2001. Cholinergic regulation of sea urchin embryonic and larval development. Ross Fiziol Zh Im I M Sechenova 87(11):1548-1556. PMID:11822358
- Buznikov GA, Nikitina LA, Bezuglov VV, Lauder JM, Padilla S, Slotkin TA. 2001. An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae. Environ Health Perspect 109(7):651-661. PMID:11485862
- Garcia SJ, Seidler FJ, Crumpton TL, Slotkin TA. 2001. Does the developmental neurotoxicity of chlorpyrifos involve glial targets? Macromolecule synthesis, adenylyl cyclase signaling, nuclear transcription factors, and formation of reactive oxygen in C6 glioma cells. Brain Res 891(1-2):54-68. PMID:11164809
- Levin ED, Addy N, Nakajima A, Christopher NC, Seidler FJ, Slotkin TA. 2001. Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Brain Res Dev Brain Res 130(1):83-89. PMID:11557096
- Navarro HA, Basta PV, Seidler FJ, Slotkin TA. 2001. Neonatal chlorpyrifos administration elicits deficits in immune function in adulthood: a neural effect?. Brain Res Dev Brain Res 130(2):249-252. PMID:11675126
- Raines KW, Seidler FJ, Slotkin TA. 2001. Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos. Brain Res Dev Brain Res 130(1):65-72. PMID:11557094
- Seidler FJ, Slotkin TA, Qiao D. 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(9):909-913. PMID:11673119 PMCID:PMC1240440
- Slotkin TA, Cousins MM, Tate CA, Seidler FJ. 2001. Persistent cholinergic presynaptic deficits after neonatal chlorpyrifos exposure. Brain Res 902(2):229-243. PMID:11384617
2000
- Auman JT, Seidler FJ, Slotkin TA. 2000. Neonatal chlorpyrifos exposure targets multiple proteins governing the hepatic adenylyl cyclase signaling cascade: implications for neurotoxicity. Brain Res Dev Brain Res 121(1):19-27. PMID:10837889
- Crumpton TL, Seidler FJ, Slotkin TA. 2000. Developmental neurotoxicity of chlorpyrifos in vivo and in vitro: effects on nuclear transcription factors involved in cell replication and differentiation. Brain Res 857(1-2):87-98. PMID:10700556
- Crumpton TL, Seidler FJ, Slotkin TA. 2000. Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos?. Brain Res Dev Brain Res 121(2):189-195. PMID:10876031
- 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. Brain Res Dev Brain Res 121(2):179-187. PMID:10876030