Skip to main content

Advertisement

Log in

In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats

  • Reproductive Toxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

This study was carried out to investigate the effect of in utero exposure to the cholinotoxicants, nicotine and chlorpyrifos, alone or in combination on neurobehavioral alterations and neuronal morphology latter in adult age. In the present study, 90 days old (corresponding to a human adult age) male and female offspring rats were evaluated for neurobehavioral, and neuropathological alterations following maternal, gestational exposure to nicotine and chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate), alone and in combination. Female Sprague-Dawley rats (300–350 g) with timed-pregnancy were treated with nicotine (3.3 mg/kg/day, in bacteriostatic water via s.c. implantation of mini osmotic pump), chlorpyrifos (1.0 mg/kg, daily, dermal, in 75% ethanol, 1.0 ml/kg) or a combination of both chemicals, on gestational days (GD) 4–20. Control animals received bacteriostatic water via s.c. implantation of mini osmotic pump and dermal application of 70% ethanol. The offspring at postnatal day (PND) 90 were evaluated for neurobehavioral performance, changes in the activity of plasma butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), and neuropathological alterations in the brain. Neurobehavioral evaluations included beam-walk score, beam-walk time, incline plane performance and forepaw grip time. Male and female offspring from mothers treated with nicotine and CPF, alone or in combination showed impairments in the performance of neurobehavioral tests, indicating sensorimotor deficits. Female offspring from mothers treated with a combination of nicotine and chlorpyrifos showed significant increase in plasma BChE activity. Brain regional AChE activity showed differential increases in male and female offspring. Brainstem and cerebellum of female offspring from mothers treated with nicotine or chlorpyrifos, alone or in combination showed increased AChE activity, whereas brainstem of male offspring from mothers treated with nicotine alone or a combination of nicotine and chlorpyrifos showed increase in AChE activity. Also, male offspring exposed in utero to nicotine exhibited increased AChE activity. Histopathological evaluations using cresyl violet staining showed a decrease in surviving Purkinje neurons in the cerebellum in offspring of all treatments groups. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer (GCL) of cerebellum following all exposures. These results indicate that in utero exposure to nicotine and chlorpyrifos, alone and in combination produced significant sensorimotor deficits in male and female offspring, differential increase in brain AChE activity, a decrease in the surviving neurons and an increased expression of GFAP in cerebellum in adult offspring rats at a corresponding human adult age. Collectively, this study demonstrates that maternal exposure to environmental neurotoxic chemicals, i.e., nicotine and chlorpyrifos leads to developmental abnormalities in the offspring that persist latter into adulthood.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdel-Rahman A, Dechkovskaia A, Mehta-Simmons H, Guan X, Khan W, Abou-Donia M (2003) Increase expression of glial fibrillary acidic pron 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

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Rahman A, Dechkovskaia AM, Mehta-Simmons H, Sutton JM, Guan X, Khan WA, Abou-Donia M (2004) Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads to persistently elevated expression of glial fibrillary acidic protein in cerebellum of the offspring in late puberty. Arch Toxicol 78:467–476

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Rahman A, Dechkovskaia AM, Sutton JM, Chen WC, Guan X, Khan WA, Abou-Donia M (2005) Maternal exposure to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty. Toxicology 209:245–261

    Article  PubMed  CAS  Google Scholar 

  • Abou-Donia MB (2003) Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health 58:484–497

    Article  PubMed  CAS  Google Scholar 

  • Abou-Donia MB, Wilmarth KR (1995) The joint action of chlorpyrifos and safrotin on development of delayed neurotoxicity in the hen. Toxicologist 15:205

    Google Scholar 

  • Abou-Donia MB, Abdel-Rahman AA, Abou-Donia SM, Jensen KF (1998) Dose-response study of propetamphos/chlorpyrifos delayed neurotoxicity in the hen. Toxicologist 42:343

    Google Scholar 

  • Abou-Donia MB, Goldstein LB, Jones KH, Abdel-Rehman AA, Damodran TV, Dechkovskaia AM, Bullman SL, Amir BE, Khan WA (2001) Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination. Toxicol Sci 60:305–314

    Article  PubMed  CAS  Google Scholar 

  • Abu-Qare Aw, Abdel-Rahman A, Brownie C, Kishk AM, Abou-Donia MB (2001) Inhibition of cholinesterase enzymes following a single dermal dose of chlorpyrifos and methyl parathion, alone and in combination, in pregnant rats. J Toxicol Environ Health 63:173–189

    Article  Google Scholar 

  • Adriani W, Spijker S, Deroche-Gamonet V, Laviola G, LeMoal M, Smit AB, Piazza V (2003) Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats. J Neurosci 23:4712–4716

    PubMed  CAS  Google Scholar 

  • Ahlsen G, Rosengren L, Belfrage M, Palm A, Haglid K, Hamberger A, Gillberg C (1993) Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiat 15:734–743

    Article  Google Scholar 

  • Altman J, Bayer SA (1990) Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 301:365–381

    Article  PubMed  CAS  Google Scholar 

  • Andres C, Seidman S, Beeri R, (1998) Transgenic acetylcholinesterase induces enlargemaent of murine neuromuscular junctions but leaves spinal synapses intact. Neurochem Int 32:449–456

    Article  PubMed  CAS  Google Scholar 

  • Andersen CS, Andersen AB, Finger S (1991) Neurological correlates of unilateral and bilateral “strokes” of the middle cerebral artery in the rat. Physiol Behav 50:263–269

    Article  PubMed  CAS  Google Scholar 

  • Atarashi R, Sakaguchi S, Shigematsu K, Arima K, Okimura N, Yaguchi N, Li A, Kopacek J, Katamine S (2001) Abnormal activation of glial cells in the brains of prion protein-deficient mice ectopically expressing prion protein-like protein, PrPLP/Dp1. Mol Med 7:803–809

    PubMed  CAS  Google Scholar 

  • Bagchi D, Bagchi M, Hassoun EA, Stohs SJ (1995) In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase by selected pesticide. Toxicology 104:129–140

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Benowitz NL (1996) Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 36:597–661

    Article  PubMed  CAS  Google Scholar 

  • Bhagwat SV, Vijayasarthy C, Raza H, Mullick J, Avadhani NG (1998) Preferential effects of nicotine and 4-(N-Methyl-N-nitrosamino)-1-(3-propyl)-1-butanone on mitochondrial glutathione-S-transferase A4–4 induction and increased oxidative stress in the rat brain. Biochem Pharmacol 56:831–839

    Article  PubMed  CAS  Google Scholar 

  • Bigbee JW, Sharma KV, Chan ELP, Bogler O (2000) Evidence for the direct role of acetylcholinesterase in neurite outgrowth in primary dorsal root ganglion neurons. Brain Res 861:354–362

    Article  PubMed  CAS  Google Scholar 

  • Booze RM, Welch MA, Wood ML, Billings KA, Apple SA, Mactutus CF (1999) Behavioral sensitization following repeated intravenous nicotine administration: gender differences and gonadal hormones. Pharmacol Biochem Behav 64:827–839

    Article  PubMed  CAS  Google Scholar 

  • Brimijoin S, Koenigsberger C (1999) Cholinesterases in neural development: new findings and toxicological implications. Environ Health Perspect 107(Suppl 1):59–64

    Article  PubMed  CAS  Google Scholar 

  • Butrum D, Silverstein FS (1993) Excitotic injury stimulates glial fibrillary acidic protein mRNA expression in perinatal rat brain. Exp Neurol 121:127–132

    Article  PubMed  Google Scholar 

  • Calderon FH, von Bernhardi R, De Ferrari G, Luza S, Aldunate R, Inestrosa NC (1998) Toxic effects of acetylcholinesterase on neuronal and Glial-like cells in vitro. Mol Psychiatry 3:247–255

    Article  PubMed  CAS  Google Scholar 

  • Capodicasa JR, Scapellato ML, Moretto A, Caroldi S, Lotti M (1991) Chlorprifos-induced polyneuropathy. Arch Toxicol 65:150–155

    Article  PubMed  CAS  Google Scholar 

  • Centers for Disease Control and Prevention (2001) Women and smoking: a report of the surgeon general. US Department of Health and Human Services, Public Health Service, Office of the Surgeon General, Washington

  • Clarke C, Clarke K, Muneyyirci J, Azmitia E, Whitaker-Azmitia PM (1996) Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100. Dev Brain Res 91:268–273

    Article  CAS  Google Scholar 

  • Clegg DJ, van Gemret M (1999) Determination of the reference dose for chlorpyrifos: proceedings of an expert panel. J Toxicol Environ Health B 2:211–255

    Article  CAS  Google Scholar 

  • Collins SL, Montano R, Izenwasser S (2004) Nicotine treatment produces persistent increases in amphetamine-stimulated locomotor activity in periadolescent male but not female or adult male rats. Dev Brain Res 153:175–187

    Article  CAS  Google Scholar 

  • Damodaran TV, Jones KH, Patel AG, Abou-Donia MB (2003) Sarin (nerve agent BG)-induced differential expression of mRNA coding for the acetylcholinesterase gene in the rat central nervous system. Biochem Pharmacol 65:2041–2047

    Article  PubMed  CAS  Google Scholar 

  • Day T, Greenfield SA (2003) A peptide derived from acetylcholinestearse induces neuronal cell death: characterisation of possible mechanisms. Exp Brain Res 153:334–342

    Article  PubMed  CAS  Google Scholar 

  • Ebrahim SH, Floyd RL, Merritt RK, Decoufle P, Holtzman D (2000) Trends in pregnancy-related smoking rates in the United States, 1987–1996. J Am Med Assoc 283:361–366

    Article  CAS  Google Scholar 

  • Elliott BM, Faraday MM, Phillips JM, Grunberg NE (2004) Effects of nicotine on elevated pulse maze and locomotor activity in male and female adolescent and adult rats. Pharmacol Biochem Behav 77:21–28

    Article  PubMed  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetycholinesterase activity. Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  • Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:2047–2066

    Article  Google Scholar 

  • Fattore L, Puddu MC, Picciau S, Cappai A, Fratta W, Serra GP, Spiga S (2002) Astroglial in vivo response to cocaine in mouse dentate gyrus: a quantitative and qualitative analysis by confocal microscopy. Neuroscience 110:1–6

    Article  PubMed  CAS  Google Scholar 

  • Fenske RA, Black KG, Elkner KP, Lee C, Methner MM, Soto R (1990) Potential exposure and health risks of infants following indoor residential pesticide applications. Am J Public Health 80:689–693

    Article  PubMed  CAS  Google Scholar 

  • Fergusson DM, Woodward LJ, Horwood LJ (1998) Maternal smoking during pregnancy and psychiatric adjustment in late adolescence. Arch Gen Psychiatry 55:721–727

    Article  PubMed  CAS  Google Scholar 

  • Fikes JD, Zachary JF, Parker AJ, Beasley R (1992) Clinical, biochemical, electrophysiologic, and histlogic assessment of chlorpyrifos-induced delayed neuropathy in the cat. Neurotoxicology 13:663–678

    PubMed  CAS  Google Scholar 

  • Floyd RL, Rimer BK, Giovino GA, Mullen PD, Sullivan SE (1993) A review of smoking in pregnancy: effects on pregnancy outcomes and cessation efforts. Annu Rev Public Health 14:379–411

    Article  PubMed  CAS  Google Scholar 

  • Garcia SJ, Seidler FJ, Qiao D, Slotkin TA (2002) Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein. Dev Brain Res 133:151–161

    Article  CAS  Google Scholar 

  • Goldstein LB (1993) Beam-walking in rats: measurement of motor recovery after injury to the cerebral cortex. Neurosci Protocol 10:1–13

    Google Scholar 

  • Guan ZZ, Yu WF, Nordberg A (2003) Dual effects of nicotine on oxidative stress and neuroprotection in PC 12 cells. Neurochem Int 43:243–249

    Article  PubMed  CAS  Google Scholar 

  • Harrod SB, Mactutus CF, Bennet K, Hasselrot U, Wu G, Welch M, Booze RM (2004) Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors. Pharmacol Biochem Behav 78:581–592

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, Khurdayan VK, Goody RJ, Nath A, Saria A, Pauly JR (2003) Selective vulnerability of cerebellar granular neuroblasts and the progeny to drugs with abuse liability. Cerebellum 2:184–195

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann D, Hoffmann I (1997) The changing cigarette, 1950–1995. J Toxicol Environ Health 50:35–56

    Article  Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821

    PubMed  CAS  Google Scholar 

  • Huff RA, Corcoran JJ, Anderson JK, Abou-Donia MB (1994) Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum. J Pharmacol Exp Ther 269:329–335

    PubMed  CAS  Google Scholar 

  • 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 26:95–101

    Article  PubMed  CAS  Google Scholar 

  • John S, Kale M, Rathore N, Bhatnagar D (2001) Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes. J Nutr Biochem 12:500–504

    Article  PubMed  CAS  Google Scholar 

  • Johnson JG, Cohen P, Pine DS, Klein DF, Kasen S, Brook JS (2000) Association between cigarette smoking and anxiety disorders during adolescence and early adulthood. J Am Med Assoc 284:2348–2351

    Article  CAS  Google Scholar 

  • Kanyt L, Stolerman IP, Chandler CJ, Saigusa CJ, Pogun S (1999) Influence of sex and female hormones on nicotine-induced changes in locomotor activity in rats. Pharmacol Biochem Behav 62:179–187

    Article  PubMed  CAS  Google Scholar 

  • Khan WA, Dechkovskaia AM, Herrick EA, Jones KH, Abou-Donia MB (2000) Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervous system of the rat. Toxicol Sci 57:112–120

    Article  PubMed  CAS  Google Scholar 

  • Kristjansdottir R, Uvebrant P, Rosengren L (2001) Glial fibrillary acidic protein and neurofilament in the children with cerebral white matter abnormalities. Neuropediatrics 32:307–312

    Article  PubMed  CAS  Google Scholar 

  • Law KL, Stroud LR, LaGasse LL, Niaura R, Liu J, Lester BM (2003) Smoking during pregnancy and newborn neurobehavior. Pediatrics 111:1318–1323

    Article  PubMed  Google Scholar 

  • Lie Y, He H-Y, Zhang X-J (2002) Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci Res 42:261–268

    Article  PubMed  Google Scholar 

  • Lemus R, Abdelghani A (2000) Chlorpyrifos: an unwelcome pesticide in our homes. Rev Environ Health 15:421–433

    PubMed  CAS  Google Scholar 

  • 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 24:733–741

    Article  PubMed  CAS  Google Scholar 

  • Liedtke W, Edelman W, Bieri PL, Chin FC, Cowen NJ, Kucherlpati R, Raine CS (1996) GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 17:607–615

    Article  PubMed  CAS  Google Scholar 

  • Liptakova S, Velisek L, Veliskova H, Moshe SL (2000) Effect of ganaxolone on flurothyl seizures in developing rats. Epilepsia 41:788–793

    Article  PubMed  CAS  Google Scholar 

  • Little AR, Benkovic SA, Miller DB, O’Callaghan JP (2002) Chemically induced neuronal damage and gliosis: enhanced expression of the proinflammatory chemokine, monocyte chemoattractant protein MCP-1), without a corresponding increase in proinflammatory cytokines. Neuroscience 115:307–320

    Article  PubMed  CAS  Google Scholar 

  • Lotti M, Moretto A, Zoppellari R, Dainese R, Rizzuto N, Barusco G (1986) Inhibition of lymphocytic neuropathy target esterase predicts the development of organophosphate-induced delayed polyneuropathy. Arch Toxicol 59:176–179

    Article  PubMed  CAS  Google Scholar 

  • Martin JC, Becker RF (1970) The effects of nicotine administration in utero upon activity in the rat. Psychopharmacol Sci 19:59–60

    Google Scholar 

  • Mayer JP, Hawkins B, Todd R (1990) A randomized evaluation of smoking cessation interventions for pregnant women at a WIC clinic. Am J Public Health 80:76–78

    PubMed  CAS  Google Scholar 

  • Naeye RL (1992) Cognitive and behavioral abnormalities in children whose mothers smoked cigarettes during pregnancy. J Dev Behav Pediatr 13:425–428

    PubMed  CAS  Google Scholar 

  • Nordberg A, Zhang X, Fredriksson A, Eriksson P (1991) Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behavior in adult mice. Dev Brain Res 63:201–207

    Article  CAS  Google Scholar 

  • O’Callaghan JP (1993) Quantitative features of reactive gliosis following toxicant-induced damage of the CNS. Ann NY Acad Sci 679:195–210

    Article  PubMed  Google Scholar 

  • Penky M, Stannes K, Eliasson C, Betsholtz C, Janigro D (1998) Impaired induction of blood-brain barrier properties in aortic endothelial cells by astrocytes from GFAP-deficient mice. Glia 22:390–400

    Article  PubMed  Google Scholar 

  • Pletnikov MV, Rubin SA, Vasudevan K, Moran TH, Carbone KM (1999) Develomental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism. Behav Brain Res 100:43–50

    Article  PubMed  CAS  Google Scholar 

  • Pope CN (1999) Organophosphorus pesticides: do they all have the same mechanism of toxicity? J Toxicol Environ Health B 2:161–181

    Article  CAS  Google Scholar 

  • Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological functions. Trends Neurosci 20:570–577

    Article  PubMed  CAS  Google Scholar 

  • Romero RD, Chen WJ (2004) Gender-related response in open-field activity following developmental nicotine exposure in rats. Pharmacol Biochem Behav 78:675–681

    Article  PubMed  CAS  Google Scholar 

  • Roy TS, Seidler FJ, Slotkin TA (2002) Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex. J Pharmacol Exp Ther 300:124–133

    Article  PubMed  CAS  Google Scholar 

  • Saberna G, Saez-Valero J, Li Q-X, Czech C, Beyreuther K, Masters CL, McLean CA, Small DH (1998) Acetylcholineaserase is increased in the brains of transgenic mice expressing the C-terminal fragment (CT100) of the amyloid protein precurser of Alzheimer’s Disease. J Neurochem 71:723–731

    Article  PubMed  Google Scholar 

  • Shibuki K, Gomi H, Chen L, Bao S, Kim JJ, Wakatsuki H, Fujisaki T, Fujimoto K, Katoh A, Ikeda T, Chen C, Thompson RF, Itohara S (1996) Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice. Neuron 16:587–599

    Article  PubMed  CAS  Google Scholar 

  • Slotkin TA (1998) Fetal nicotine or cocaine exposure: which is worse? J Pharmacol Exp Ther 285:931–945

    PubMed  CAS  Google Scholar 

  • Slotkin TA, Orband-Miller L, Queen KL (1986) Development of [3H] nicotine binding sites in the brain regions of rats exposed to nicotine prenatal via maternal injection or infusions. J Pharmacol Exp Ther 242:232–237

    Google Scholar 

  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner LH, Provenzo MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  PubMed  CAS  Google Scholar 

  • Sternfeld M, Ming G, Song H, Sela K, Timberg R, Poo M, Soreq H (1998) Acetylcholinesterase enhances neurite growth and synapse development through alternative contributions of its hydrolytic capacity, core protein, and variable C termini. J Neurosci 18:1240–1249

    PubMed  CAS  Google Scholar 

  • Trauth JA, Seidler FJ, Slotkin TA (2000) Persistent and delayed behavioral changes after nicotine treatment in adolescent rats. Brain Res 880:167–172

    Article  PubMed  CAS  Google Scholar 

  • Tsuneishi S, Takada S, Motoike T, Ohashi T, Sano K, Nakamura H (1991) Effects of dexamethasone on the expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein genes in developing rat brain. Dev Brain Res 61:117–123

    Article  CAS  Google Scholar 

  • US Environmental Protection Agency (2000) Administrator’s announcement. http://www.epa.gov/pesticides/announcements6800html

  • Vaglenova J, Birru S, Pandiella NM, Breese CR (2004) An assessment of the long-term developmental and behavioral teratogenecity of prenatal nicotine exposure. Behav Brain Res 150:159–170

    Article  PubMed  CAS  Google Scholar 

  • Verma RS, Srivastava N (2001) Chlorpyrifos induced alterations in levels of thiobarbituric acid reactive substances and glutathione in rat brain. Indian J Exp Biol 39:174–177

    PubMed  CAS  Google Scholar 

  • Yang L, Heng-Yi H, Zhang XJ (2002) Increased expression of intranuclear AchE involved in apoptosis of SK-N-SH cells. Neurosci Res 42:261–268

    Article  PubMed  CAS  Google Scholar 

  • Yonemori F, Yamaguchi T, Yamada H, Tamura A (1998) Evaluation of a motor deficit after chronic focal cerebral ischemia in rats. J Cereb Blood Flow Metab 18:1099–1106

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Liu C, Miao H, Gong Z, Nordberg A (1998) Postnatal changes of nicotininc acetylcholine receptor in rat brain. Int J Neurosci 16:507–518

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The work was accomplished through the financial support provided by the US EPA (EPA grant # R829399-01-0). The views, opinion and/or findings contained in this study are those of the authors and should not be construed as an official U.S. EPA policy or decision unless so designated by other documents.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohamed B. Abou-Donia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abou-Donia, M.B., Khan, W.A., Dechkovskaia, A.M. et al. In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats. Arch Toxicol 80, 620–631 (2006). https://doi.org/10.1007/s00204-006-0077-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-006-0077-1

Keywords

Navigation