Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice.

Autor:	Curtis MA; Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, USA., Dhamsania RK; College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.; Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA., Branco RC; Laney Graduate School, Emory University, Atlanta, GA 30322, USA.; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Guo JD; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA., Creeden J; Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA., Neifer KL; Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, USA., Black CA; Laney Graduate School, Emory University, Atlanta, GA 30322, USA.; Schiemer School of Psychology and Biblical Counseling, Truett McConnell University, Cleveland, GA 30528, USA., Winokur EJ; College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.; Department of Cognitive Science, University of California San Diego, La Jolla, CA 92093, USA., Andari E; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.; Department of Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA., Dias BG; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.; Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.; Division of Endocrinology, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.; Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA 90027, USA., Liu RC; Department of Biology, Emory University, Atlanta, GA 30322, USA.; Center for Translational Social Neuroscience, Emory University, Atlanta, GA 30322, USA., Gourley SL; Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA.; Emory National Primate Research Center, Atlanta, GA 30329, USA., Miller GW; Department of Environmental Health, Emory Rollins School of Public Health, Atlanta, GA 30322, USA.; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA., Burkett JP; Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, USA.; Department of Environmental Health, Emory Rollins School of Public Health, Atlanta, GA 30322, USA.
Jazyk:	angličtina
Zdroj:	PNAS nexus [PNAS Nexus] 2023 Apr 25; Vol. 2 (4), pp. pgad085. Date of Electronic Publication: 2023 Apr 25 (Print Publication: 2023).
DOI:	10.1093/pnasnexus/pgad085
Abstrakt:	Neurodevelopmental disorders (NDDs) are a widespread and growing public health challenge, affecting as many as 17% of children in the United States. Recent epidemiological studies have implicated ambient exposure to pyrethroid pesticides during pregnancy in the risk for NDDs in the unborn child. Using a litter-based, independent discovery-replication cohort design, we exposed mouse dams orally during pregnancy and lactation to the Environmental Protection Agency's reference pyrethroid, deltamethrin, at 3 mg/kg, a concentration well below the benchmark dose used for regulatory guidance. The resulting offspring were tested using behavioral and molecular methods targeting behavioral phenotypes relevant to autism and NDD, as well as changes to the striatal dopamine system. Low-dose developmental exposure to the pyrethroid deltamethrin (DPE) decreased pup vocalizations, increased repetitive behaviors, and impaired both fear conditioning and operant conditioning. Compared with control mice, DPE mice had greater total striatal dopamine, dopamine metabolites, and stimulated dopamine release, but no difference in vesicular dopamine capacity or protein markers of dopamine vesicles. Dopamine transporter protein levels were increased in DPE mice, but not temporal dopamine reuptake. Striatal medium spiny neurons showed changes in electrophysiological properties consistent with a compensatory decrease in neuronal excitability. Combined with previous findings, these results implicate DPE as a direct cause of an NDD-relevant behavioral phenotype and striatal dopamine dysfunction in mice and implicate the cytosolic compartment as the location of excess striatal dopamine. (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)
Databáze:	MEDLINE
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