[Frontiers in Bioscience E4, 2745-2753, June 1, 2012]

[Frontiers in Bioscience E4, 2745-2753, June 1, 2012]

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

Markus Gantert^1,3, Pawel Kreczmanski², Elke Kuypers³, Reint Jellema³, Eveline Strackx³, Nina Bastian⁴, Antonio W.D. Gavilanes³, Luc J.I. Zimmermann³, Yves Garnier¹, Christoph Schmitz^2,5, Boris W. Kramer³

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

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods: 3.1. Experimental setup of the animal study; 3.2. Tissue processing; 3.3. Immunohistochemistry; 3.4. Nissl staining; 3.5. Qualitative and quantitative histological analysis; 3.6. Photography; 3.7. Statistical analysis
4. Results
5. Discussion
6. Acknowledgements
7. References

1. 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.