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, Markus ; Kreczmanski, Pawel ; Kuypers, Elke ; Jellema, Reint ; Strackx, Eveline ; Bastian, Nina ; Gavilanes, Antonio W. D. ; Zimmermann, Luc J I ; Garnier, Yves ; Schmitz, Christoph ; Kramer, Boris W. / Effects of in utero endotoxemia on the ovine fetal brain : a model for schizophrenia?. In: Frontiers in Bioscience, Elite edition. 2012 ; Vol. 1, No. 4. pp. 2845-53.
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Gantert, M, Kreczmanski, P, Kuypers, E, Jellema, R, Strackx, E, Bastian, N, Gavilanes, AWD, Zimmermann, LJI, Garnier, Y, Schmitz, C & Kramer, BW 2012, 'Effects of in utero endotoxemia on the ovine fetal brain: a model for schizophrenia?', Frontiers in Bioscience, Elite edition, vol. 1, no. 4, pp. 2845-53.

Effects of in utero endotoxemia on the ovine fetal brain : a model for schizophrenia? / Gantert, Markus; Kreczmanski, Pawel; Kuypers, Elke; Jellema, Reint; Strackx, Eveline; Bastian, Nina; Gavilanes, Antonio W. D.; Zimmermann, Luc J I; Garnier, Yves; Schmitz, Christoph; Kramer, Boris W.

In: Frontiers in Bioscience, Elite edition, Vol. 1, No. 4, 01.06.2012, p. 2845-53.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Effects of in utero endotoxemia on the ovine fetal brain

T2 - a model for schizophrenia?

AU - Gantert, Markus

AU - Kreczmanski, Pawel

AU - Kuypers, Elke

AU - Jellema, Reint

AU - Strackx, Eveline

AU - Bastian, Nina

AU - Gavilanes, Antonio W. D.

AU - Zimmermann, Luc J I

AU - Garnier, Yves

AU - Schmitz, Christoph

AU - Kramer, Boris W

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N2 - 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.

AB - 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.

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KW - Brain

KW - Disease Models, Animal

KW - Endotoxemia

KW - Female

KW - Immunohistochemistry

KW - Pregnancy

KW - Schizophrenia

KW - Sheep

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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JO - Frontiers in Bioscience, Elite edition

JF - Frontiers in Bioscience, Elite edition

SN - 1945-0494

IS - 4

ER -

Gantert M, Kreczmanski P, Kuypers E, Jellema R, Strackx E, Bastian N et al. Effects of in utero endotoxemia on the ovine fetal brain: a model for schizophrenia? Frontiers in Bioscience, Elite edition. 2012 Jun 1;1(4):2845-53.