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Developmental neurotoxic effects of two pesticides: behavior and biomolecular studies on chlorpyrifos and carbaryl
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
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2015 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 288, no 3, 429-438 p.Article in journal (Refereed) Published
Abstract [en]

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5 mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0 mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8–12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

Place, publisher, year, edition, pages
2015. Vol. 288, no 3, 429-438 p.
Keyword [en]
Developmental neurotoxicology, Chlorpyrifos, Carbaryl, Acetylcholinesterase, Protein, Behavior
National Category
Other Biological Topics
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-261192DOI: 10.1016/j.taap.2015.08.014ISI: 000363083600015PubMedID: 26314619OAI: oai:DiVA.org:uu-261192DiVA: diva2:851118
Funder
EU, FP7, Seventh Framework Programme, 282957
Available from: 2015-09-03 Created: 2015-08-31 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
Open this publication in new window or tab >>Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The focus of this thesis was to investigate developmental neurotoxic effects of different persistent and non-persistent environmental pollutants, alone or in binary mixtures, when exposure occurs during a critical period of brain development, in mice. The compounds investigated included a perfluorinated compound, perfluorohexane sulphonate (PFHxS), and four different pesticides, endosulfan, cypermethrin, chlorpyrifos and carbaryl.

Both persistent and non-persistent pollutants are detected in the environment and in humans, which shows that exposure to these compounds is occurring in real life. Humans can therefore be exposed to various pollutants during their whole lifetime, starting from the gestational period to adulthood. Furthermore, exposure to environmental pollutants is rarely exclusive to a single compound, but rather occurs through combinations of various pollutants present in the environment. Exposure to environmental pollutants during human brain development have been suggested to be a possible cause for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous studies have shown that chemicals can induce irreversible disorders in brain function when exposure to these chemicals occurs during a critical defined period of the brain development known as the brain growth spurt (BGS). The BGS is characterized by a rapid growth and development of the immature brain. In humans, and mice, this period also overlaps the lactation period indicating that newborns and toddlers can be exposed via mothers’ milk as well.

This thesis has shown that a single oral exposure to PFHxS, endosulfan, cypermethrin, chlorpyrifos or carbaryl can induce developmental neurotoxic effects in mice, when exposure occurs during a critical period of brain development. These effects are manifested as persistent altered adult spontaneous behavior in a novel home environment, modified habituation, altered susceptibility of the cholinergic system and changed levels of neuroproteins in the mouse brain. Furthermore, a single neonatal co-exposure to a binary mixture of carbaryl/chlorpyrifos or PFHxS/endosulfan can interact and exacerbate the adult behavioral effects. These effects were seen at dosages were the single compound did not elicit a response or induced a much weaker behavioral effect. This indicates that risk assessments conducted on single compounds might underestimate interaction effects of mixtures when co-exposed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1283
Keyword
Brain, Neonatal, Mixtures, Cholinergic system, Organochlorines, Pyrethroids, Organophosphates, Carbamates, Insecticides, PFCs, PFAAs, PFHxS, Endosulfan, Cypermethrin, Chlorpyrifos, Carbaryl
National Category
Natural Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-261742 (URN)978-91-554-9326-4 (ISBN)
Public defence
2015-10-23, Zootissalen, EBC, Villavägen 9, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2015-10-02 Created: 2015-09-03 Last updated: 2015-10-05

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Lee, IwaEriksson, PerFredriksson, AndersBuratovic, SonjaViberg, Henrik

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