Nurr1 is not essential for the development of prepulse inhibition deficits induced by prenatal immune activation

Stéphanie Vuillermot, Joram Feldon, Urs Meyer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Inflammation-induced disruption of fetal neurodevelopmental processes has been linked to the precipitation of long-lasting behavioral abnormalities and associated neuropathology. Recent longitudinal investigations in prenatal immune activation models have revealed developmental correspondences between the ontogeny of specific dopaminergic neuropathology and the postnatal onset of distinct forms of dopamine-dependent functional abnormalities implicated in schizophrenia. Two examples of such developmental correspondences are increased expression of the orphan nuclear receptor Nurr1 (NR4A2) in ventral midbrain areas and disruption of prepulse inhibition of the acoustic startle reflex, with both the neuroanatomical and behavioral effects emerging only in adult but not pre-pubertal subjects exposed to prenatal maternal inflammation. In the present study, we tested the hypothesis that Nurr1 may be a critical molecular mediator of prepulse inhibition deficits induced by prenatal immune activation. To this end, we compared the effects of prenatal immune challenge on adult PPI in wild-type (wt) mice and mice with a heterozygous constitutive deletion of Nurr1 (Nurr1+/-) using a well established mouse model of maternal immune activation by exposure to the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic acid). We found that prenatal poly(I:C) treatment on gestation day 9 was similarly effective in disrupting prepulse inhibition in adult wt and Nurr1+/- mice. Prenatal poly(I:C) treatment also generally increased midbrain Nurr1-positive cells and counteracted the genetically driven Nurr1 deficit in the substantia nigra. Our data thus suggest that at least under the present experimental conditions, Nurr1 is not essential for the development of prepulse inhibition deficits induced by prenatal immune activation.

Original languageEnglish
Pages (from-to)1316-1321
Number of pages6
JournalBrain, Behavior, and Immunity
Volume25
Issue number7
DOIs
StatePublished - Oct 2011
Externally publishedYes

Funding

FundersFunder number
Eidgenössische Technische Hochschule Zürich– 11 07/03
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung3100AO-100309, 100309, 3100AO-116719

    Keywords

    • Cytokines
    • Dopamine
    • Infection
    • Maternal immune activation
    • Schizophrenia

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