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Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms

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Abstract

It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.

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Funding

This study was funded by the European Commission (FP7-ENV-2011 no. 282957, DENAMIC project), the Ministerio de Ciencia e Innovación (SAF2011-23051), and the Consellería de Educación de la Generalitat Valenciana (PROMETEOII/2014/033).

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  1. Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Eduardo Primo Yufera, 3, 46012, Valencia, Spain

    B. Gómez-Giménez, V. Felipo, A. Cabrera-Pastor, A. Agustí, V. Hernández-Rabaza & M. Llansola

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  1. B. Gómez-Giménez
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  2. V. Felipo
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  3. A. Cabrera-Pastor
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  4. A. Agustí
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  5. V. Hernández-Rabaza
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  6. M. Llansola
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Correspondence to V. Felipo.

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“All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.” European Union for the protection of animals used for scientific purposes (Directive 2010/63/EU). “All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (CIPF).”

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Gómez-Giménez, B., Felipo, V., Cabrera-Pastor, A. et al. Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms. Neurotox Res 33, 247–258 (2018). https://doi.org/10.1007/s12640-017-9823-9

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  • DOI: https://doi.org/10.1007/s12640-017-9823-9

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