Intrauterine inflammation induces sex-specific effects on neuroinflammation, white matter, and behavior

Ryan Makinson, Kelsey Lloyd, Aditya Rayasam, Sarah McKee, Amy Brown, Guillermo Barila, Nicola Grissom, Robert George, Matt Marini, Zsuzsanna Fabry, Michal Elovitz, Teresa M. Reyes

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Exposure to inflammation during pregnancy has been linked to adverse neurodevelopmental consequences for the offspring. One common route through which a developing fetus is exposed to inflammation is with intrauterine inflammation. To that end, we utilized an animal model of intrauterine inflammation (IUI; intrauterine lipopolysaccharide (LPS) administration, 50 µg, E15) to assess placental and fetal brain inflammatory responses, white matter integrity, anxiety-related behaviors (elevated zero maze, light dark box, open field), microglial counts, and the CNS cytokine response to an acute injection of LPS in both males and females. These studies revealed that for multiple endpoints (fetal brain cytokine levels, cytokine response to adult LPS challenge) male IUI offspring were uniquely affected by intrauterine inflammation, while for other endpoints (behavior, microglial number) both sexes were similarly affected. These data advance our understanding of sex-specific effects of early life exposure to inflammation in a translationally- relevant model.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalBrain, Behavior, and Immunity
Volume66
DOIs
StatePublished - Nov 2017

Keywords

  • Anxiety
  • Cytokine
  • Locomotor
  • Placenta
  • Prefrontal cortex
  • Prenatal inflammation
  • Sex difference
  • White matter

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