Maternal immune activation with high molecular weight poly(I:C) in Wistar rats leads to elevated immune cell chemoattractants

  • Author Footnotes
    1 Joint first authors.
    Amelia M. Brown
    Footnotes
    1 Joint first authors.
    Affiliations
    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia
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  • Author Footnotes
    1 Joint first authors.
    Illya Conn
    Footnotes
    1 Joint first authors.
    Affiliations
    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia

    School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia

    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia
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  • Danny Boerrigter
    Affiliations
    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia
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  • Cynthia Shannon Weickert
    Affiliations
    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia

    School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia

    Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, New York 13210, USA
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  • Tertia D. Purves-Tyson
    Correspondence
    Corresponding author at: Neuroscience Research Australia, Schizophrenia Research Laboratory, 139 Barker Street, Margarete Ainsworth Building, Level 5, Randwick, NSW 2031, Australia.
    Affiliations
    Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia

    School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
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  • Author Footnotes
    1 Joint first authors.

      Highlights

      • Maternal immune activation (MIA) with 4 mg/kg high molecular weight (HMW)-poly(I:C), selected from a dose response curve in nulliparous rats, induced maternal sickness and weight loss without disrupting pregnancy.
      • The immune response elicited in pregnant Wistar rat dams on GD19 by 4 mg/kg HMW-poly(I:C) included increases in pro-and anti-inflammatory serum cytokines and immune cell chemoattractants – MIP-3α, MIP-1α, CXCL1, M-CSF, MCP-1, G-CSF.
      • Adult male Wister rats have higher peripheral cytokines as compared to adult female Wistar rats.
      • MIA did not lead to significant alterations in peripheral cytokines in male or female offspring.
      • MIA did not lead to a difference in the proportion of offspring that could be classified as having a pattern of elevated cytokines.

      Abstract

      Maternal immune activation (MIA) with poly(I:C) is a preclinical paradigm for schizophrenia and autism research. Methodological variations, including poly(I:C) molecular weight, contribute to inconsistencies in behavioural and molecular outcomes. We established in Wistar rats that 4 mg/kg high molecular weight (HMW)-poly(I:C) on GD19 induces maternal sickness, smaller litters and maternal elevations of serum cytokines, including increases in monocyte chemoattractants. In adult offspring, we found that males have higher serum cytokines than females, and MIA did not alter peripheral cytokines in either sex. Our study will contribute to the effective use of the MIA model to elucidate the neurobiology of neurodevelopmental disorders.

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