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dc.contributor.authorFrye, Richard E.
dc.contributor.authorCakir, Janet
dc.contributor.authorRose, Shannon
dc.contributor.authorDelhey, Leanna
dc.contributor.authorBennuri, Sirish C.
dc.contributor.authorTippett, Marie
dc.contributor.authorPalmer, Raymond F.
dc.contributor.authorAustin, Christine
dc.contributor.authorCurtin, Paul
dc.contributor.authorArora, Manish
dc.date.accessioned2021-02-06T01:53:55Z
dc.date.available2021-02-06T01:53:55Z
dc.date.issued2020-07
dc.identifier.citationFrye, R.E., Cakir, J., Rose, S. et al. Early life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder. Transl Psychiatry 10, 223 (2020).
dc.identifier.issn2158-3188
dc.identifier.pmid32636364
dc.identifier.doi10.1038/s41398-020-00905-3
dc.identifier.urihttp://hdl.handle.net/10150/651788
dc.description.abstractNeurodevelopmental regression (NDR) is a subtype of autism spectrum disorder (ASD) that manifests as loss of previously acquired developmental milestones. Early life dysregulation of nutritional metals and/or exposure to toxic metals have been associated with ASD, but the underlying biological mechanisms by which metals influence neurodevelopment remain unclear. We hypothesize that metals influences neurodevelopment through dysregulation of bioenergetics. Prenatal and early postnatal metal exposures were measured using validated tooth-matrix biomarkers in 27 ASD cases (13 with NDR) and 7 typically-developing (TD) controls. Mitochondrial respiration and glycolysis were measured in peripheral blood mononuclear cells using the Seahorse XF96. Children with ASD demonstrated lower prenatal and postnatal Copper (Cu) and prenatal Nickel concentrations and Copper-to-Zinc (Cu/Zn) ratio as compared with TD children. Children with ASD and NDR showed greater metal-related disruption of cellular bioenergetics than children with ASD without NDR. For children with ASD and NDR mitochondrial respiration decreased as prenatal Manganese concentration increased and increased as prenatal Zinc concentration increased; glycolysis decreased with increased exposure to prenatal Manganese and Lead and postnatal Manganese. For children with ASD without a history of NDR, glycolysis increased with increased postnatal exposure to Tin. Language and communication scores in children with ASD were positively related to prenatal Cu exposure and Cu/Zn ratio. This study suggests that prenatal nutritional metals may be important for neurodevelopment in children with ASD, and that exposure to toxic metals and differences in nutritional metal exposures is associated with dysregulation of cellular bioenergetics, particularly in the NDR subtype of ASD.
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.rightsCopyright © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleEarly life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder
dc.typeArticle
dc.typetext
dc.contributor.departmentUniv Arizona, Coll Med Phoenix
dc.identifier.journalTRANSLATIONAL PSYCHIATRY
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
dc.eprint.versionFinal published version
refterms.dateFOA2021-02-06T01:53:55Z


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Copyright © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License.