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Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity.
Neurotox Res. 2018 Nov; 34(4):820-833.NR

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.

Authors+Show Affiliations

Department of Clinical Analysis, Federal University of Santa Catarina, Florianópolis, Brazil. dirleise@yahoo.com.br. Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil. dirleise@yahoo.com.br. Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil. dirleise@yahoo.com.br.Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil.Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29859004

Citation

Colle, Dirleise, et al. "Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation By Inducing Oxidative Stress: New Insights On Pesticide-Induced Neurodevelopmental Toxicity." Neurotoxicity Research, vol. 34, no. 4, 2018, pp. 820-833.
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. 2018;34(4):820-833.
Colle, D., Farina, M., Ceccatelli, S., & Raciti, M. (2018). Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity. Neurotoxicity Research, 34(4), 820-833. https://doi.org/10.1007/s12640-018-9916-0
Colle D, 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. 2018;34(4):820-833. PubMed PMID: 29859004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity. AU - Colle,Dirleise, AU - Farina,Marcelo, AU - Ceccatelli,Sandra, AU - Raciti,Marilena, Y1 - 2018/06/01/ PY - 2018/02/23/received PY - 2018/05/21/accepted PY - 2018/04/25/revised PY - 2018/6/3/pubmed PY - 2018/11/27/medline PY - 2018/6/3/entrez KW - Brain development KW - Maneb KW - N-acetylcysteine KW - Neural stem cells KW - Oxidative stress KW - Paraquat SP - 820 EP - 833 JF - Neurotoxicity research JO - Neurotox Res VL - 34 IS - 4 N2 - 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. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/29859004/Paraquat_and_Maneb_Exposure_Alters_Rat_Neural_Stem_Cell_Proliferation_by_Inducing_Oxidative_Stress:_New_Insights_on_Pesticide_Induced_Neurodevelopmental_Toxicity_ L2 - https://dx.doi.org/10.1007/s12640-018-9916-0 DB - PRIME DP - Unbound Medicine ER -