Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice

Brain Behav Immun. 2008 May;22(4):469-86. doi: 10.1016/j.bbi.2007.09.012. Epub 2007 Nov 26.

Abstract

Maternal infection during pregnancy increases the risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. This association appears to be critically dependent on the precise prenatal timing. However, the extent to which distinct adult psychopathological and neuropathological traits may be sensitive to the precise times of prenatal immune activation remains to be further characterized. Here, we evaluated in a mouse model of prenatal immune challenge by the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyIC), whether prenatal immune activation in early/middle and late gestation may influence the susceptibility to some of the critical cognitive, pharmacological, and neuroanatomical dysfunctions implicated in schizophrenia and autism. We revealed that PolyIC-induced prenatal immune challenge on gestation day (GD) 9 but not GD17 significantly impaired sensorimotor gating and reduced prefrontal dopamine D1 receptors in adulthood, whereas prenatal immune activation specifically in late gestation impaired working memory, potentiated the locomotor reaction to the NMDA-receptor antagonist dizocilpine, and reduced hippocampal NMDA-receptor subunit 1 expression. On the other hand, potentiation of the locomotor reaction to the dopamine-receptor agonist amphetamine and reduction in Reelin- and Parvalbumin-expressing prefrontal neurons emerged independently of the precise times of prenatal immune challenge. Our findings thus highlight that prenatal immune challenge during early/middle and late fetal development in mice leads to distinct brain and behavioral pathological symptom clusters in adulthood. Further examination and evaluation of in utero immune challenge at different times of gestation may provide important new insight into the neuroimmunological and neuropathological mechanisms underlying the segregation of different symptom clusters in heterogeneous neuropsychiatric disorders such as schizophrenia and autism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Age Factors
  • Amphetamines / pharmacology
  • Animals
  • Autistic Disorder / immunology*
  • Autistic Disorder / pathology
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Central Nervous System Stimulants / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Interferon Inducers / immunology
  • Interferon Inducers / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Parvalbumins / metabolism
  • Poly I-C / immunology
  • Poly I-C / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology*
  • Prenatal Exposure Delayed Effects / pathology
  • Receptors, Dopamine D1 / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Reflex, Startle / immunology
  • Schizophrenia / immunology*
  • Schizophrenia / pathology
  • Serine Endopeptidases / metabolism
  • Specific Pathogen-Free Organisms
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amphetamines
  • Cell Adhesion Molecules, Neuronal
  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Extracellular Matrix Proteins
  • Interferon Inducers
  • NMDA receptor A1
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid
  • Dizocilpine Maleate
  • Serine Endopeptidases
  • reelin protein
  • Poly I-C