Skip to main content

Advertisement

SpringerLink
Log in

Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity

  • ORIGINAL ARTICLE
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Pesticide exposure has been linked to the pathogenesis of neurodevelopmental and neurodegenerative disorders including autism spectrum disorders, attention deficit/hyperactivity, and Parkinson’s disease (PD). Developmental exposure to pesticides, even at low concentrations not harmful for the adult brain, can lead to neuronal loss and functional deficits. It has been shown that prenatal or early postnatal exposure to the herbicide paraquat (PQ) and the fungicide maneb (MB), alone or in combination, causes permanent toxicity in the nigrostriatal dopamine system, supporting the idea that early exposure to these pesticides may contribute to the pathophysiology of PD. However, the mechanisms mediating PQ and MB developmental neurotoxicity are not yet understood. Therefore, we investigated the neurotoxic effect of low concentrations of PQ and MB in primary cultures of rat embryonic neural stem cells (NSCs), with particular focus on cell proliferation and oxidative stress. Exposure to PQ alone or in combination with MB (PQ + MB) led to a significant decrease in cell proliferation, while the cell death rate was not affected. Consistently, PQ + MB exposure altered the expression of major genes regulating the cell cycle, namely cyclin D1, cyclin D2, Rb1, and p19. Moreover, PQ and PQ + MB exposures increased the reactive oxygen species (ROS) production that could be neutralized upon N-acetylcysteine (NAC) treatment. Notably, in the presence of NAC, Rb1 expression was normalized and a normal cell proliferation pattern could be restored. These findings suggest that exposure to PQ + MB impairs NSCs proliferation by mechanisms involving alterations in the redox state.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Ali SF, LeBel CP, Bondy SC (1992) Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13:637–648

    CAS  PubMed  Google Scholar 

  • Andersen HR, Debes F, Wohlfahrt-Veje C, Murata K, Grandjean P (2015) Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age. Neurotoxicol Teratol 47:1–9

    Article  CAS  Google Scholar 

  • Barlow BK, Thiruchelvam MJ, Bennice L, Cory-Slechta DA, Ballatori N, Richfield EK (2003) Increased synaptosomal dopamine content and brain concentration of paraquat produced by selective dithiocarbamates. J Neurochem 85:1075–1086

    Article  CAS  Google Scholar 

  • Barlow BK, Richfield EK, Cory-Slechta DA, Thiruchelvam M (2004) A fetal risk factor for Parkinson’s disease. Dev Neurosci 26:11–23

    Article  CAS  Google Scholar 

  • Barlow BK, Lee DW, Cory-Slechta DA, Opanashuk LA (2005) Modulation of antioxidant defense systems by the environmental pesticide maneb in dopaminergic cells. Neurotoxicology 26:63–75

    Article  CAS  Google Scholar 

  • Barlow BK, Cory-Slechta DA, Richfield EK, Thiruchelvam M (2007) The gestational environment and Parkinson’s disease: evidence for neurodevelopmental origins of a neurodegenerative disorder. Reprod Toxicol 23:457–470

    Article  CAS  Google Scholar 

  • Barouki R, Gluckman PD, Grandjean P, Hanson M, Heindel JJ (2012) Developmental origins of non-communicable disease: implications for research and public health. Environ Health 11:42

    Article  Google Scholar 

  • Bearer CF (1998) Biomarkers in pediatric environmental health: a cross-cutting issue. Environ Health Perspect 106:813–816

    PubMed  PubMed Central  Google Scholar 

  • Ben-Porath I, Weinberg RA (2005) The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37:961–976

    Article  CAS  Google Scholar 

  • Bose R, Moors M, Tofighi R, Cascant A, Hermanson O, Ceccatelli S (2010) Glucocorticoids induce long-lasting effects in neural stem cells resulting in senescence-related alterations. Cell Death Dis 1(11):e92

    Article  CAS  Google Scholar 

  • Bose R, Onishchenko N, Edoff K, Janson Lang AM, Ceccatelli S (2012) Inherited effects of low-dose exposure to methylmercury in neural stem cells. Toxicol Sci 130:383–390

    Article  CAS  Google Scholar 

  • Burova E, Borodkina A, Shatrova A, Nikolsky N (2013) Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium. Oxidative Med Cell Longev 2013:474931

    Article  Google Scholar 

  • Calderbank A (1968) The bipyridylium herbicides. Adv Pest Control Res 8:127–235

    CAS  PubMed  Google Scholar 

  • Cam H, Dynlacht BD (2003) Emerging roles for E2F: beyond the G1/S transition and DNA replication. Cancer Cell 3:311–316

    Article  CAS  Google Scholar 

  • Canepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, Ogara MF (2007) INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life 59:419–426

    Article  CAS  Google Scholar 

  • Castello PR, Drechsel DA, Patel M (2007) Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem 282:14186–14193

    Article  CAS  Google Scholar 

  • Cattani D, Cesconetto PA, Tavares MK, Parisotto EB, De Oliveira PA, Rieg CEH, Leite MC, Prediger RDS, Wendt NC, Razzera G, Filho DW, Zamoner A (2017) Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: implication of glutamate excitotoxicity and oxidative stress. Toxicology 387:67–80

    Article  CAS  Google Scholar 

  • Claudio L, Kwa WC, Russell AL, Wallinga D (2000) Testing methods for developmental neurotoxicity of environmental chemicals. Toxicol Appl Pharmacol 164:1–14

    Article  CAS  Google Scholar 

  • Cory-Slechta DA, Thiruchelvam M, Barlow BK, Richfield EK (2005) Developmental pesticide models of the Parkinson disease phenotype. Environ Health Perspect 113:1263–1270

    Article  CAS  Google Scholar 

  • Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B (2009) Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 169:919–926

    Article  Google Scholar 

  • Day BJ, Patel M, Calavetta L, Chang LY, Stamler JS (1999) A mechanism of paraquat toxicity involving nitric oxide synthase. Proc Natl Acad Sci U S A 96:12760–12765

    Article  CAS  Google Scholar 

  • De Felice A, Greco A, Calamandrei G, Minghetti L (2016) Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism. J Neuroinflammation 13:149

    Article  Google Scholar 

  • Dennery PA (2007) Effects of oxidative stress on embryonic development. Birth Defects Res C Embryo Today 81:155–162

    Article  CAS  Google Scholar 

  • Dringen R, Pawlowski PG, Hirrlinger J (2005) Peroxide detoxification by brain cells. J Neurosci Res 79:157–165

    Article  CAS  Google Scholar 

  • Duronio RJ, Xiong Y (2013) Signaling pathways that control cell proliferation. Cold Spring Harb Perspect Biol 5:a008904

    Article  Google Scholar 

  • Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12:2245–2262

    Article  CAS  Google Scholar 

  • Edoff K, Raciti M, Moors M, Sundstrom E, Ceccatelli S (2017) Gestational age and sex influence the susceptibility of human neural progenitor cells to low levels of MeHg. Neurotox Res 32(4):683–693

    Article  CAS  Google Scholar 

  • Eubig PA, Aguiar A, Schantz SL (2010) Lead and PCBs as risk factors for attention deficit/hyperactivity disorder. Environ Health Perspect 118:1654–1667

    Article  CAS  Google Scholar 

  • EUR-Lex (2007) Judgment of the Court of First Instance: European Directive 91/414/EEC case T-229/04. Available from http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:62004TJ0229:EN:NOT/ (accessed in 28 Sept 2017)

  • Farina M, Campos F, Vendrell I, Berenguer J, Barzi M, Pons S, Sunol C (2009) Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol Sci 112:416–426

    Article  CAS  Google Scholar 

  • Ferriero DM, Miller SP (2010) Imaging selective vulnerability in the developing nervous system. J Anat 217:429–435

    Article  Google Scholar 

  • Froes Asmus CI, Camara VM, Landrigan PJ, Claudio L (2016) A systematic review of children’s environmental health in Brazil. Ann Glob Health 82:132–148

    Article  Google Scholar 

  • Giacinti C, Giordano A (2006) RB and cell cycle progression. Oncogene 25:5220–5227

    Article  CAS  Google Scholar 

  • Gonzalez-Alzaga B, Hernandez AF, Rodriguez-Barranco M, Gomez I, Aguilar-Garduno C, Lopez-Flores I, Parron T, Lacasana M (2015) Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from south-eastern Spain. Environ Int 85:229–237

    Article  CAS  Google Scholar 

  • Guo YL, Chakraborty S, Rajan SS, Wang R, Huang F (2010) Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal. Stem Cells Dev 19:1321–1331

    Article  CAS  Google Scholar 

  • Guo BQ, Yan CH, Cai SZ, Yuan XB, Shen XM (2013) Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex. Toxicology 304:57–68

    Article  CAS  Google Scholar 

  • Harari R, Julvez J, Murata K, Barr D, Bellinger DC, Debes F, Grandjean P (2010) Neurobehavioral deficits and increased blood pressure in school-age children prenatally exposed to pesticides. Environ Health Perspect 118:890–896

    Article  CAS  Google Scholar 

  • Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ (1995) Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol 15:2672–2681

    Article  CAS  Google Scholar 

  • Homem CC, Repic M, Knoblich JA (2015) Proliferation control in neural stem and progenitor cells. Nat Rev Neurosci 16:647–659

    Article  CAS  Google Scholar 

  • Kang MJ, Gil SJ, Koh HC (2009) Paraquat induces alternation of the dopamine catabolic pathways and glutathione levels in the substantia nigra of mice. Toxicol Lett 188:148–152

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Lee JJ, Kim BC, Park MJ, Lee YS, Kim YN, Lee BL, Lee JS (2011) PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation. Cell Death Differ 18:666–677

    Article  CAS  Google Scholar 

  • Li B, He X, Sun Y (2016) Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats. Mol BioSyst 12:3088–3097

    Article  CAS  Google Scholar 

  • Liddell JR, Dringen R, Crack PJ, Robinson SR (2006) Glutathione peroxidase 1 and a high cellular glutathione concentration are essential for effective organic hydroperoxide detoxification in astrocytes. Glia 54:873–879

    Article  Google Scholar 

  • Lopez-Diazguerrero NE, Lopez-Araiza H, Conde-Perezprina JC, Bucio L, Cardenas-Aguayo MC, Ventura JL, Covarrubias L, Gutierrez-Ruiz MC, Zentella A, Konigsberg M (2006) Bcl-2 protects against oxidative stress while inducing premature senescence. Free Radic Biol Med 40:1161–1169

    Article  CAS  Google Scholar 

  • Maciel-Baron LA, Moreno-Blas D, Morales-Rosales SL, Gonzalez-Puertos VY, Lopez-Diazguerrero NE, Torres C, Castro-Obregon S, Konigsberg M (2017) Cellular senescence, neurological function, and redox state. Antioxid Redox Signal. https://doi.org/10.1089/ars.2017.7112

    Article  Google Scholar 

  • Mascarelli A (2013) Growing up with pesticides. Science 341:740–741

    Article  CAS  Google Scholar 

  • Mercola JM (2017) Paraquat—banned in EU while US increasing use of this toxic killer. Available from https://articles.mercola.com/sites/articles/archive/2017/01/03/paraquat-banned-in-32-countries.aspx / (accessed 26 Oct 2017)

  • Meyerson M, Harlow E (1994) Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol 14:2077–2086

    Article  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  • Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31:1287–1312

    Article  CAS  Google Scholar 

  • Prakash J, Yadav SK, Chouhan S, Singh SP (2013) Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism. Neurochem Res 38:972–980

    Article  CAS  Google Scholar 

  • Rice D, Barone SJ (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108:511–533

    PubMed  PubMed Central  Google Scholar 

  • Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C (2007) Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect 115:1482–1489

    PubMed  PubMed Central  Google Scholar 

  • Rodier PM (1995) Developing brain as a target of toxicity. Environ Health Perspect 103:73–76

    PubMed  PubMed Central  Google Scholar 

  • Roede JR, Hansen JM, Go YM, Jones DP (2011) Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicol Sci 121(2):368–375

    Article  CAS  Google Scholar 

  • Rosa R, Sanfeliu C, Sunol C, Pomes A, Rodriguez-Farre E, Schousboe A, Frandsen A (1997) The mechanism for hexachlorocyclohexane-induced cytotoxicity and changes in intracellular Ca2+ homeostasis in cultured cerebellar granule neurons is different for the gamma- and delta-isomers. Toxicol Appl Pharmacol 142:31–39

    Article  CAS  Google Scholar 

  • Ross ME (1996) Cell division and the nervous system: regulating the cycle from neural differentiation to death. Trends Neurosci 19:62–68

    Article  CAS  Google Scholar 

  • Salas-Vidal E, Lomeli H, Castro-Obregon S, Cuervo R, Escalante-Alcalde D, Covarrubias L (1998) Reactive oxygen species participate in the control of mouse embryonic cell death. Exp Cell Res 238:136–147

    Article  CAS  Google Scholar 

  • Satyanarayana A, Kaldis P (2009) Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28:2925–2939

    Article  CAS  Google Scholar 

  • Scharffetter-Kochanek K, Wlaschek M, Brenneisen P, Schauen M, Blaudschun R, Wenk J (1997) UV-induced reactive oxygen species in photocarcinogenesis and photoaging. Biol Chem 378:1247–1257

    CAS  PubMed  Google Scholar 

  • Shackelford RE, Kaufmann WK, Paules RS (2000) Oxidative stress and cell cycle checkpoint function. Free Radic Biol Med 28:1387–1404

    Article  CAS  Google Scholar 

  • Sheldon RA, Jiang X, Francisco C, Christen S, Vexler ZS, Tauber MG, Ferriero DM (2004) Manipulation of antioxidant pathways in neonatal murine brain. Pediatr Res 56:656–662

    Article  CAS  Google Scholar 

  • Shelton JF, Hertz-Picciotto I, Pessah IN (2012) Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspect 120:944–951

    Article  Google Scholar 

  • Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, Hansen RL, Hertz-Picciotto I (2014) Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect 122:1103–1109

    Article  Google Scholar 

  • Sherr CJ (1994) G1 phase progression: cycling on cue. Cell 79:551–555

    Article  CAS  Google Scholar 

  • Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9:1149–1163

    Article  CAS  Google Scholar 

  • Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512

    Article  CAS  Google Scholar 

  • Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18:2699–2711

    Article  CAS  Google Scholar 

  • Shukla S, Singh D, Kumar V, Chauhan AK, Singh S, Ahmad I, Pandey HP, Singh C (2015) NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: crosstalk with mitochondrial dysfunction. Pestic Biochem Physiol 123:74–86

    Article  CAS  Google Scholar 

  • Singh D, Kumar V, Singh C (2017) IFN-gamma regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Mol Cell Biochem 427:133–143

    Article  CAS  Google Scholar 

  • Sonzogni SV, Ogara MF, Belluscio LM, Castillo DS, Scassa ME, Canepa ET (2014) p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation. Biochim Biophys Acta 1840:2171–2183

    Article  CAS  Google Scholar 

  • Stringari J, Nunes AK, Franco JL, Bohrer D, Garcia SC, Dafre AL, Milatovic D, Souza DO, Rocha JB, Aschner M, Farina M (2008) Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain. Toxicol Appl Pharmacol 227:147–154

    Article  CAS  Google Scholar 

  • Takahashi RN, Rogerio R, Zanin M (1989) Maneb enhances MPTP neurotoxicity in mice. Res Commun Chem Pathol Pharmacol 66:167–170

    CAS  PubMed  Google Scholar 

  • Tamm C, Duckworth J, Hermanson O, Ceccatelli S (2006) High susceptibility of neural stem cells to methylmercury toxicity: effects on cell survival and neuronal differentiation. J Neurochem 97:69–78

    Article  CAS  Google Scholar 

  • Tamm C, Duckworth JK, Hermanson O, Ceccatelli S (2008) Methylmercury inhibits differentiation of rat neural stem cells via notch signalling. Neuroreport 19:339–343

    Article  CAS  Google Scholar 

  • Temple S (2001) The development of neural stem cells. Nature 414:112–117

    Article  CAS  Google Scholar 

  • Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory-Slechta DA (2000) Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 873:225–234

    Article  CAS  Google Scholar 

  • Thiruchelvam M, Richfield EK, Goodman BM, Baggs RB, Cory-Slechta DA (2002) Developmental exposure to the pesticides paraquat and maneb and the Parkinson’s disease phenotype. Neurotoxicology 23:621–633

    Article  CAS  Google Scholar 

  • Tilson HA (1998) Developmental neurotoxicology of endocrine disruptors and pesticides: identification of information gaps and research needs. Environ Health Perspect 106:807–811

    PubMed  PubMed Central  Google Scholar 

  • Tofighi R, Moors M, Bose R, Ibrahim WN, Ceccatelli S (2011a) Neural stem cells for developmental neurotoxicity studies. Methods Mol Biol 758:67–80

    Article  CAS  Google Scholar 

  • Tofighi R, Wan Ibrahim WN, Rebellato P, Andersson PL, Uhlen P, Ceccatelli S (2011b) Non-dioxin-like polychlorinated biphenyls interfere with neuronal differentiation of embryonic neural stem cells. Toxicol Sci 124:192–201

    Article  CAS  Google Scholar 

  • Tsatmali M, Walcott EC, Crossin KL (2005) Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors. Brain Res 1040:137–150

    Article  CAS  Google Scholar 

  • Tsatmali M, Walcott EC, Makarenkova H, Crossin KL (2006) Reactive oxygen species modulate the differentiation of neurons in clonal cortical cultures. Mol Cell Neurosci 33:345–357

    Article  CAS  Google Scholar 

  • Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330

    Article  CAS  Google Scholar 

  • Wilson WW, Shapiro LP, Bradner JM, Caudle WM (2014) Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring. Neurotoxicology 44:279–287

    Article  CAS  Google Scholar 

  • Yang W, Tiffany-Castiglioni E (2005) The bipyridyl herbicide paraquat produces oxidative stress-mediated toxicity in human neuroblastoma SH-SY5Y cells: relevance to the dopaminergic pathogenesis. J Toxicol Environ Health A 68:1939–1961

    Article  CAS  Google Scholar 

Download references

Funding

The study was supported by grants from the Swedish Research Council and Karolinska Institutet and from the Brazilian Agency Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq (processes 406807/2013-2 and 402067/2015-0). D.C. acknowledges the Science Without Borders Program. M.F. is a CNPq fellowship recipient.

Author information

Authors and Affiliations

  1. Department of Clinical Analysis, Federal University of Santa Catarina, Florianópolis, Brazil

    Dirleise Colle

  2. Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil

    Dirleise Colle & Marcelo Farina

  3. Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil

    Dirleise Colle

  4. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Sandra Ceccatelli & Marilena Raciti

Authors
  1. Dirleise Colle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcelo Farina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra Ceccatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marilena Raciti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dirleise Colle.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

Experiments were approved by the local Animal Ethics Committee (Stockholm Northern Ethics Board of Animal Experimentation, ethical permission numbers: N190/14r).

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (KI).

This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Colle, D., Farina, M., Ceccatelli, S. et al. Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity. Neurotox Res 34, 820–833 (2018). https://doi.org/10.1007/s12640-018-9916-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-018-9916-0

Keywords

Search

Navigation