Dataset Information

In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.

ABSTRACT: Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.

SUBMITTER: Laugeray A

PROVIDER: S-EPMC5636066 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.

Laugeray Anthony A Herzine Ameziane A Perche Olivier O Richard Olivier O Montecot-Dubourg Céline C Menuet Arnaud A Mazaud-Guittot Séverine S Lesné Laurianne L Jegou Bernard B Mortaud Stéphane S

PloS one 20171011 10

Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 ...[more]

PMID: 29020013

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Project description:BackgroundIndoor spraying of walls and ceilings with residual insecticide remains a primary method of malaria control. Insecticide resistance in malaria vectors is a growing problem. Novel insecticides for indoor residual spraying (IRS) which can improve the control of pyrethroid resistant malaria vectors are urgently needed. Insecticide mixtures have the potential to improve efficacy or even to manage resistance in some situations but this possibility remains underexplored experimentally. Chlorfenapyr is a novel pyrrole insecticide which has shown potential to improve the control of mosquitoes which are resistant to current WHO-approved insecticides.MethodThe efficacy of IRS with chlorfenapyr applied alone or as a mixture with alpha-cypermeththrin (a pyrethroid) was evaluated in experimental huts in Cove, Southern Benin against wild free flying pyrethroid resistant Anopheles gambiae sl. Comparison was made with IRS with alpha-cypermethrin alone. Fortnightly 30-minute in situ cone bioassays were performed to assess the residual efficacy of the insecticides on the treated hut walls.ResultsSurvival rates of wild An gambiae from the Cove hut site in WHO resistance bioassays performed during the trial were >90% with permethrin and deltamethrin treated papers. Mortality of free-flying mosquitoes entering the experimental huts was 4% in the control hut. Mortality with alpha-cypermethrin IRS did not differ from the control (5%, P>0.656). The highest mortality was achieved with chlorfenapyr alone (63%). The alpha-cypermethrin + chlorfenapyr mixture killed fewer mosquitoes than chlorfenapyr alone (43% vs. 63%, P<0.001). While the cone bioassays showed a more rapid decline in residual mortality with chlorfenapyr IRS to <30% after only 2 weeks, fortnightly mortality rates of wild free-flying An gambiae entering the chlorfenapyr IRS huts were consistently high (50-70%) and prolonged, lasting over 4 months.ConclusionIRS with chlorfenapyr shows potential to significantly improve the control of malaria transmission in pyrethroid resistant areas compared to pyrethroid IRS or the mixture. Thirty minute in situ cone bioassays are not predictive of the performance of chlorfenapyr IRS under field conditions.

Project description:Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood and previous studies indicate the dopamine system plays a major role in ADHD pathogenesis. Two environmental exposures independently associated with dopaminergic dysfunction and ADHD risk include exposure to deltamethrin, a pyrethroid insecticide, and chronic stress. We hypothesized that combined neurodevelopmental exposure to both deltamethrin and corticosterone (CORT), the major stress hormone in rodents, would result in additive changes within the dopamine system. To study this, we developed a novel dual exposure paradigm and exposed pregnant C57BL/6 dams to 3 mg/kg deltamethrin through gestation and weaning, and their offspring to 25 μg/mL CORT dissolved in the drinking water through adulthood. Midbrain RNA expression as well as striatal and cortical protein expression of key dopaminergic components were investigated, in addition to ADHD-like behavioral tasks and electrochemical dopamine dynamics via fast-scan cyclic voltammetry. Given the well-described sexual dimorphism of ADHD, males and females were assessed separately. Males exposed to deltamethrin had significantly decreased midbrain Pitx3 expression, decreased cortical tyrosine hydroxylase (TH) expression, increased activity in the Y maze, and increased dopamine uptake rate in the dorsal striatum. These effects did not occur in males exposed to CORT only, or in males exposed to both deltamethrin and CORT, suggesting that CORT may attenuate these effects. Additionally, deltamethrin- and CORT-exposed females did not display these dopaminergic features, which indicates these changes are sex-specific. Our results show dopaminergic changes from the RNA through the functional level. Moreover, these data illustrate the importance of testing multiple environmental exposures together to better understand how combined exposures that occur in certain vulnerable populations could affect similar neurodevelopmental systems, as well as the importance of studying sex differences of these alterations.

Dataset Information

In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.

Publications

In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.

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