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

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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.

    Research areas

  • Animals, Brain, Disease Models, Animal, Endotoxemia, Female, Immunohistochemistry, Pregnancy, Schizophrenia, Sheep, Journal Article, Research Support, Non-U.S. Gov't
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Original languageEnglish
Pages (from-to)2845-53
Number of pages9
JournalFrontiers in Bioscience, Elite edition
Issue number4
Publication statusPublished - 1 Jun 2012