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Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos / Elizabeth L. BERG in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos Type de document : texte imprimé Auteurs : Elizabeth L. BERG, Auteur ; Tianna M. CHING, Auteur ; Donald A. BRUUN, Auteur ; Josef K. RIVERA, Auteur ; Milo CAREAGA, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Markus WÖHR, Auteur ; Pamela J. LEIN, Auteur ; Jill L. SILVERMAN, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Brain  Chlorpyrifos/toxicity  Female  Male  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Sprague-Dawley  United States  Animal models  Autism  Behavior  Chlorpyrifos  Imaging  Neurodevelopment  Pesticides  Rat  Social  Toxicology  Usv  Vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. METHODS: We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. RESULTS: These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. CONCLUSIONS: This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered. En ligne : https://dx.doi.org/10.1186/s11689-020-09342-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos [texte imprimé] / Elizabeth L. BERG, Auteur ; Tianna M. CHING, Auteur ; Donald A. BRUUN, Auteur ; Josef K. RIVERA, Auteur ; Milo CAREAGA, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Markus WÖHR, Auteur ; Pamela J. LEIN, Auteur ; Jill L. SILVERMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Autism Spectrum Disorder  Brain  Chlorpyrifos/toxicity  Female  Male  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Sprague-Dawley  United States  Animal models  Autism  Behavior  Chlorpyrifos  Imaging  Neurodevelopment  Pesticides  Rat  Social  Toxicology  Usv  Vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. METHODS: We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. RESULTS: These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. CONCLUSIONS: This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered. En ligne : https://dx.doi.org/10.1186/s11689-020-09342-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573