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Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia

Molecular Psychiatry volume 15, pages 372–383 (2010)Cite this article

Abstract

It has been hypothesized that the maternal immune response to infection may influence fetal brain development and lead to schizophrenia. Animal experimentation has supported this notion by demonstrating altered sensorimotor gating (prepulse inhibition, PPI) in adult rats prenatally exposed to an immune challenge. In the present study, pregnant rats were exposed to the bacterial endotoxin lipopolysaccharide (LPS) throughout gestation and the offspring were examined by evaluating the PPI, dopaminergic function, brain protein expression and cytokine serum levels from weaning to late adulthood. Prenatal LPS exposure induced a deficit in PPI that emerged at ‘puberty’ and that persisted throughout adult life. This prenatal insult caused age-specific changes in accumbal dopamine levels and in synaptophysin expression in the frontal cortex. Moreover, serum cytokine levels were altered in an age- and cytokine-dependent manner. Here we show that prenatal LPS administration throughout pregnancy causes maturation-dependent PPI deficits and age-dependent alterations in dopamine activity, as well as in synaptophysin expression and cytokine levels.

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Acknowledgements

We thank Rufino Fernández for his excellent technical assistance during the course of this research and María González for generating the HPLC data. This work was supported by the Fondo de Investigación Sanitaria (FIS, grant number 01/1138), Fundació La Marató de TV3 (grant number 014931) and the Comunidad de Madrid (grant number 08.5/0020/2001).

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  1. E Romero

    Present address: 3Current address: Institut de Génomique Fonctionnelle de Lyon, UMR CNRS 5242 INRA 1288, IFR128, Ecole Normale Supérieure de Lyon, 46 allée d′Italie, 69364 Lyon cedex 07, France.,

Authors and Affiliations

  1. Functional and Systems Neurobiology Department, Group of Neuroimmunology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain

    E Romero, C Guaza & J Borrell

  2. Unit of Histology, Faculty of Medicine, Autonomous University of Barcelona, Bellaterra, Spain

    B Castellano

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Correspondence to J Borrell.

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Romero, E., Guaza, C., Castellano, B. et al. Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia. Mol Psychiatry 15, 372–383 (2010). https://doi.org/10.1038/mp.2008.44

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