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Deficits in Bioenergetics and Impaired Immune Response in Granulocytes From Children With Autism
Open accessAbstract
Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)–induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2–related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.
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“There are presently several lines of evidence indicating oxidative stress and mitochondrial dysfunction are prevalent in individuals with ASD [3,10,11,12,13,14,15,16].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [12]
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Metadata
- Authors
- Napoli, E., Wong, S., Hertz-Picciotto, I., & Giulivi, C.
- Affiliations
- Department of Molecular Biosciences, School of Veterinary Medicine,
- Department of Public Health Sciences, School of Medicine, and
- University of California, Davis (US)
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2014-05-01
- Volume
- 133
- Issue
- 5
- Pages
- e1405-e1410
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- PMC
- PMC4006429
- OpenAlex
- W2156732833
- Cited by
- 117
- References
- 78
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 5 · 2021: 9 · 2020: 13 · 2019: 5 · 2018: 15 · 2017: 10 · 2016: 12 · 2015: 10 · 2014: 6
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- PEDIATRICS (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Simons Foundation (271406)
- Simons Foundation Autism Research Initiative
- National Institutes of Health (ES011269)
- National Institute of Environmental Health Sciences (R01-ES011269, ES020392, R01ES020392, ES015359, R01ES015359, ES011269, P01ES011269, 271406)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- autism spectrum disorder, mitochondrial dysfunction, bioenergetics, granulocytes, oxidative phosphorylation, respiratory burst, NADPH oxidase, NF-E2-related factor 2, oxidative stress, mitochondrial DNA deletions, reactive oxygen species, children
- MeSH terms
- Child, Child Development Disorders, Pervasive, Energy Metabolism, Granulocytes, Humans, Oxidative Phosphorylation, Oxygen Consumption, Superoxides
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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