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The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans.

Publication ,  Journal Article
Zhou, H; Lin, Y; Zhao, W; Teng, Y; Cui, Y; Wang, T; Li, C; Jiang, Y-H; Zhang, JJ; Wang, Y
Published in: Environmental pollution (Barking, Essex : 1987)
December 2020

Previous studies have associated the risk of autism spectrum disorder (ASD) with increased exposures to metals and metalloids such as arsenic. In this study, we used an animal-to-human translational strategy to identify key molecular changes that potentially mediated the effects of arsenic exposures on ASD development. In a previously established rat model, we have induced autistic behaviors in rat pups with gestational arsenic exposures (10 and 45 μg/L As2O3 in drinking water). Neuronal apoptosis and the associated epigenetic dysregulations in frontal cortex were assayed to screen potential mediating pathways, which were subsequently validated with qPCR, western blotting, and immunohistochemistry analyses. Furthermore, the identified pathway, along with serum levels of 26 elements including arsenic, were characterized in a case-control study with 21 ASD children and 21 age-matched healthy controls. In animals, we found that arsenic exposures caused difficulties of social interaction and increased stereotypic behaviors in a dose-dependent manner, accompanied by increased neuronal apoptosis and upregulation of Hipk2-p53 pathway in the frontal cortex. In humans, we found that serum levels of Hipk2 and p53 were 24.7 (95%CI: 8.5 to 43.4) % and 23.7 (95%CI: 10.5 to 38.5) % higher in ASD children than in healthy controls. ASD children had significantly higher serum levels of 15 elements, among which arsenic, silicon, strontium, and vanadium were positively associated with both Hipk2 and p53. Results from both the rat arsenic exposure and human case-control studies suggest a likely role of Hipk2-p53 pathway in ASD development induced by exposures to environmental pollutants such as arsenic.

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Published In

Environmental pollution (Barking, Essex : 1987)

DOI

EISSN

1873-6424

ISSN

0269-7491

Publication Date

December 2020

Volume

267

Start / End Page

115568

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Rats
  • Protein Serine-Threonine Kinases
  • Humans
  • Environmental Sciences
  • Child
  • Case-Control Studies
  • Carrier Proteins
  • Autistic Disorder
  • Autism Spectrum Disorder
 

Citation

APA
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ICMJE
MLA
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Zhou, H., Lin, Y., Zhao, W., Teng, Y., Cui, Y., Wang, T., … Wang, Y. (2020). The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans. Environmental Pollution (Barking, Essex : 1987), 267, 115568. https://doi.org/10.1016/j.envpol.2020.115568
Zhou, Hao, Yan Lin, Weiqing Zhao, Yanbo Teng, Yuxia Cui, Tianqi Wang, Chunpei Li, Yong-Hui Jiang, Junfeng Jim Zhang, and Yi Wang. “The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans.Environmental Pollution (Barking, Essex : 1987) 267 (December 2020): 115568. https://doi.org/10.1016/j.envpol.2020.115568.
Zhou H, Lin Y, Zhao W, Teng Y, Cui Y, Wang T, et al. The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans. Environmental pollution (Barking, Essex : 1987). 2020 Dec;267:115568.
Zhou, Hao, et al. “The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans.Environmental Pollution (Barking, Essex : 1987), vol. 267, Dec. 2020, p. 115568. Epmc, doi:10.1016/j.envpol.2020.115568.
Zhou H, Lin Y, Zhao W, Teng Y, Cui Y, Wang T, Li C, Jiang Y-H, Zhang JJ, Wang Y. The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans. Environmental pollution (Barking, Essex : 1987). 2020 Dec;267:115568.
Journal cover image

Published In

Environmental pollution (Barking, Essex : 1987)

DOI

EISSN

1873-6424

ISSN

0269-7491

Publication Date

December 2020

Volume

267

Start / End Page

115568

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Rats
  • Protein Serine-Threonine Kinases
  • Humans
  • Environmental Sciences
  • Child
  • Case-Control Studies
  • Carrier Proteins
  • Autistic Disorder
  • Autism Spectrum Disorder