Effects of in utero endotoxemia on the ovine fetal brain: a model for schizophrenia?

Markus Gantert, Pawel Kreczmanski, Elke Kuypers, Reint Jellema, Eveline Strackx, Nina Bastian, Antonio W. D. Gavilanes, Luc J I Zimmermann, Yves Garnier, Christoph Schmitz, Boris W Kramer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Infections during pregnancy can adversely affect the development of the fetal brain. This may contribute to disease processes such as schizophrenia in later life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC), particularly in GABA-ergic interneurons, play a role in the pathogenesis of schizophrenia. We hypothesized that exposure to infection during pregnancy could result in cyto-architectural changes in the fetal ACC, similar to the pathogenesis seen in schizophrenia. Fetal sheep of 110 days GA (term=150 days GA) received an intravenous injection of 100 ng or 500 ng lipopolysaccharide (LPS) or saline as control. After delivery at 113 days GA, the cyto-architecture of the cingulate cortex (CC) was examined by immunohistochemistry. High dose LPS exposure resulted in a decreased density of GFAP-, calbindin D-28K- and parvalbumin-immunoreactive cells in the CC. In addition, these cells and calretinin-immunoreactive cells showed a changed morphology with reduced cell processes. This study provides further evidence that intra-uterine endotoxemia can induce changes in the fetal brain which correspond with changes seen in schizophrenia.

Original languageEnglish
Pages (from-to)2845-53
Number of pages9
JournalFrontiers in Bioscience, Elite edition
Volume1
Issue number4
Publication statusPublished - 1 Jun 2012

Keywords

  • Animals
  • Brain
  • Disease Models, Animal
  • Endotoxemia
  • Female
  • Immunohistochemistry
  • Pregnancy
  • Schizophrenia
  • Sheep
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Gantert, M., Kreczmanski, P., Kuypers, E., Jellema, R., Strackx, E., Bastian, N., Gavilanes, A. W. D., Zimmermann, L. J. I., Garnier, Y., Schmitz, C., & Kramer, B. W. (2012). Effects of in utero endotoxemia on the ovine fetal brain: a model for schizophrenia? Frontiers in Bioscience, Elite edition, 1(4), 2845-53.