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Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice.
Curtis, Melissa A; Dhamsania, Rohan K; Branco, Rachel C; Guo, Ji-Dong; Creeden, Justin; Neifer, Kari L; Black, Carlie A; Winokur, Emily J; Andari, Elissar; Dias, Brian G; Liu, Robert C; Gourley, Shannon L; Miller, Gary W; Burkett, James P.
Afiliação
  • 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.
  • Branco RC; Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA.
  • Guo JD; Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
  • Creeden J; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Neifer KL; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Black CA; Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
  • Winokur EJ; Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, USA.
  • Andari E; Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
  • Dias BG; Schiemer School of Psychology and Biblical Counseling, Truett McConnell University, Cleveland, GA 30528, USA.
  • Liu RC; College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.
  • Gourley SL; Department of Cognitive Science, University of California San Diego, La Jolla, CA 92093, USA.
  • Miller GW; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Burkett JP; Department of Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
PNAS Nexus ; 2(4): pgad085, 2023 Apr.
Article em En | MEDLINE | ID: mdl-37113978
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article