Maternal exposure to prostaglandin E2 modifies expression of Wnt genes in mouse brain: an autism connection

Ravneet Rai-Bhogal, Christine Wong, Ashby Kissoondoyal, Jennilee Davidson, Hongyan Li, Dorota A. Crawford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
49 Downloads (Pure)

Abstract

Prostaglandin E2 (PGE2) is a lipid signaling molecule important for brain development and function. Various genetic and environmental factors can influence the level of PGE2 and increase the risk of developing Autism Spectrum Disorder (ASD). We have previously shown that in neuronal cell lines and mouse brain, PGE2 can interfere with the Wnt canonical pathway, which is essential during early brain development. Higher levels of PGE2 increased Wnt-dependent motility and proliferation of neuroectodermal stem cells, and modified the expression of Wnt genes previously linked to autism disorders. We also recently established a cross-talk between these two pathways in the prenatal mouse brain lacking PGE2 producing enzyme (COX-/-). The current study complements the published data and reveals that PGE2 signaling also converges with the Wnt canonical pathway in the developing mouse brain after maternal exposure to PGE2 at the onset of neurogenesis. We found significant changes in the expression level of Wnt-target genes, Mmp7, Wnt2, and Wnt3a, during prenatal and early postnatal stages. Interestingly, we observed variability in the expression level of these genes between genetically-identical pups within the same pregnancy. Furthermore, we found that all the affected genes have been previously associated with disorders of the central nervous system, including autism. We determined that prenatal exposure to PGE2 affects the Wnt pathway at the level of β-catenin, the major downstream regulator of Wnt-dependent gene transcription. We discuss how these results add new knowledge into the molecular mechanisms by which PGE2 may interfere with neuronal development during critical periods.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalBiochemistry and Biophysics Reports
Volume14
DOIs
Publication statusPublished - 1 Jul 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Autism Spectrum Disorder
  • Gene expression
  • Lipids
  • Prostaglandin E
  • Wnt signaling pathway
  • β-catenin

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