The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology

Urs Meyer, Myriel Nyffeler, Andrea Engler, Adrian Urwyler, Manfred Schedlowski, Irene Knuesel, Kay Yan Benjamin Yee, Joram Feldon

Research output: Journal article publicationJournal articleAcademic researchpeer-review

542 Citations (Scopus)

Abstract

Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro- and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.
Original languageEnglish
Pages (from-to)4752-4762
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number18
DOIs
Publication statusPublished - 7 Sep 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Cytokines
  • Inflammation
  • Neurogenesis
  • Prenatal
  • Reelin

ASJC Scopus subject areas

  • Neuroscience(all)

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