Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin

Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

doi:10.1016/j.tox.2015.06.010

Cited by 64 publications

(35 citation statements)

References 86 publications

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“…Oxidative stress and dysregulated immune responses are implicated in organophosphate related toxicity and pathogenesis of autism spectrum disorder, suggesting a possible mode of action 13. Coexposing mice shortly after birth to cypermethrin (a pyrethroid) and endosulfan altered levels of neuroproteins and resulted in neurobehavioral abnormalities 12. Gene expression of mouse cortical neurons was altered by certain fungicides and resembled transcriptional changes thought to underlie development of autism spectrum disorder 214.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental in vivo and in vitro studies of autism121314 suggested changes in neuroprotein levels, altered gene expression, and neurobehavioral abnormalities after exposure to certain pesticides 1214. For example, when the organophosphate chlorpyrifos was administered prenatally at subtoxic levels to a mouse model that displays several behavioral traits related to the autism spectrum, male offspring showed delayed motor function maturation and enhanced behavioral features associated with autism spectrum disorder 13…”

Section: Introductionmentioning

confidence: 99%

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Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Ehrenstein

Ling

Cui

et al. 2019

BMJ

208

165

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Objective To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder. Design Population based case-control study. Setting California’s main agricultural region, Central Valley, using 1998-2010 birth data from the Office of Vital Statistics. Population 2961 individuals with a diagnosis of autism spectrum disorder based on the Diagnostic and Statistical Manual of Mental Disorders , fourth edition, revised (up to 31 December 2013), including 445 with intellectual disability comorbidity, were identified through records maintained at the California Department of Developmental Services and linked to their birth records. Controls derived from birth records were matched to cases 10:1 by sex and birth year. Exposure Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods). Main outcome measure Odds ratios and 95% confidence intervals using multivariable logistic regression were used to assess associations between pesticide exposure and autism spectrum disorder (with or without intellectual disabilities) in offspring, adjusting for confounders. Results Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances. Conclusion Findings suggest that an offspring’s risk of autism spectrum disorder increases following prenatal exposure to ambient pesticides within 2000 m of their mother’s residence during pregnancy, compared with offspring of women from the same agricultural region without such exposure. Infant exposure could further increase risks for autism spectrum disorder with comorbid intellectual disability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Ehrenstein

Ling

Cui

et al. 2019

BMJ

208

165

View full text Add to dashboard Cite

show abstract

“…Pesticides, which also contain VOCs, are also known to have neurotoxic effects, with evidence that exposure to pesticides may delay motor development (De Felice, Scattoni, Ricceri, & Calamandrei, 2015), alter neuroprotein levels (Lee, Eriksson, Fredriksson, Buratovic, & Viberg, 2015), and interfere with mechanisms related to oxidative stress (De Felice, Greco, Calamandrei, & Minghetti, 2016). Exposure to pesticides, including organophosphates (OP) (Shelton et al, 2014; D’Amelio et al, 2005), organochlorines (OC) (Roberts et al, 2007), and pyrethroids (Domingues et al, 2016), has also previously been linked to ASD.…”

Section: Introductionmentioning

confidence: 99%

Maternal Exposures Associated with Autism Spectrum Disorder in Jamaican Children

Christian

Samms‐Vaughan

Lee

et al. 2018

J Autism Dev Disord

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with poorly understood etiology. Many maternal exposures during pregnancy and breastfeeding potentially interfere with neurodevelopment. Using data from two age- and sex-matched case-control studies in Jamaica (n = 298 pairs), results of conditional logistic regression analyses suggest that maternal exposures to fever or infection (matched odds ratio (MOR) = 3.12, 95% CI 1.74-5.60), physical trauma (MOR 2.02, 95% CI 1.01-4.05), and oil-based paints (MOR 1.99, 95% CI 1.14-3.46) may be associated with ASD. Additionally, maternal exposure to oil-based paints may modify the relationship between maternal exposure to pesticides and ASD, which deepens our understanding of the association between pesticides and ASD.

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“…Taken together, our data show that Na v 1.1 is susceptible to deltamethrin modification at lower concentrations than for Na v 1.6, but this susceptibility stems from a bias toward resting modification over use-dependent, demonstrating that Na v isoforms have differential responses to the same pyrethroid treatment. With significant susceptibility to deltamethrin, Nav1.1 might be the biological link between early-life exposure to pyrethroids, impaired function of inhibitory fast-spiking interneurons (where Nav1.1 is abundantly expressed) and increased risk for neurodevelopmental disorders in the human population (Viel et al, 2015; Richardson et al, 2015; Ogiwara et al, 2007; Berkowicz et al, 2016; Dong et al, 2016; Inan et al, 2016; Jiang et al, 2013; McNally et al, 2013; Catterall et al, 2008; Lee et al, 2015). Future studies profiling activity of a broader spectrum of pyrethroids against Nav1.1 channels might generate improved EPA guidelines to prevent early-life exposure toxicity of pesticides.…”

Section: Discussionmentioning

confidence: 99%

Consequences of acute Na v 1.1 exposure to deltamethrin

et al. 2017

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Background Pyrethroid insecticides are the most popular class of insecticides in the world, despite their near-ubiquity, their effects of delaying the onset of inactivation of voltage-gated sodium (Nav) channels have not been well-evaluated in all the mammalian Nav isoforms. Objective Here we compare the well-studied Nav1.6 isoforms to the less-understood Nav1.1 in their responses to acute deltamethrin exposure. Methods We used patch-clamp electrophysiology to record sodium currents encoded by either Nav1.1 or Nav1.6 channels stably expressed in HEK293 cells. Protocols evaluating both resting and use-dependent modification were employed. Results We found that exposure of both isoforms to 10 μM deltamethrin significantly potentiated persistent and tail current densities without affecting peak transient current densities, and only Nav1.1 maintained these significant effects at 1 μM deltamethrin. Window currents increased for both as well, and while only Nav1.6 displayed changes in activation slope and V1/2 of steady-state inactivation for peak currents, V1/2 of persistent current activation was hyperpolarized of ~10 mV by deltamethrin in Nav1.1 cells. Evaluating use-dependence, we found that deltamethrin again potentiated persistent and tail current densities in both isoforms, but only Nav1.6 demonstrated use-dependent enhancement, indicating the primary deltamethrin-induced effects on Nav1.1 channels are not use-dependent. Conclusion Collectively, these data provide evidence that Nav1.1 is indeed vulnerable to deltamethrin modification at lower concentrations than Nav1.6, and this effect is primarily mediated during the resting state. General significance These findings identify Nav1.1 as a novel target of pyrethroid exposure, which has major implications for the etiology of neuropsychiatric disorders associated with loss of Nav1.1-expressing inhibitory neurons.

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Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin

Cited by 64 publications

References 86 publications

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Maternal Exposures Associated with Autism Spectrum Disorder in Jamaican Children

Consequences of acute Na v 1.1 exposure to deltamethrin

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