IMR Press / FBE / Volume 4 / Issue 8 / DOI: 10.2741/E588

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


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

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1 Department of Obstetrics and Gynaecology, Klinikum Osnabruck, Osnabruck, Germany
2 Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands
3 Department of Pediatrics, School for Oncology and Developmental Biology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands
4 Department of Ophthalmology, Bonn University Hospital, Bonn, Germany
5 Department of Neuroanatomy, Ludwig-Maximilians University, Munich, Germany

*Author to whom correspondence should be addressed.

Front. Biosci. (Elite Ed) 2012, 4(8), 2745–2753;
Published: 1 June 2012

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.

Brain development
Cingulate cortex
Animal model
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