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Impact of Maternal Immune Activation on Nonhuman Primate Prefrontal Cortex Development: Insights for Schizophrenia

  • Kari L. Hanson
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California

    MIND Institute, University of California, Davis, Davis, California
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  • Simone E. Grant
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California
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  • Lucy H. Funk
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California
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  • Author Footnotes
    1 CMS and MDB contributed equally to this work as joint senior authors.
    Cynthia M. Schumann
    Correspondence
    Address correspondence to Cynthia M. Schumann, Ph.D.
    Footnotes
    1 CMS and MDB contributed equally to this work as joint senior authors.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California

    MIND Institute, University of California, Davis, Davis, California
    Search for articles by this author
  • Author Footnotes
    1 CMS and MDB contributed equally to this work as joint senior authors.
    Melissa D. Bauman
    Correspondence
    Melissa D. Bauman, Ph.D.
    Footnotes
    1 CMS and MDB contributed equally to this work as joint senior authors.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California

    MIND Institute, University of California, Davis, Davis, California

    California National Primate Research Center, University of California, Davis, Davis, California
    Search for articles by this author
  • Author Footnotes
    1 CMS and MDB contributed equally to this work as joint senior authors.

      Abstract

      Late adolescence is a period of dynamic change in the brain as humans learn to navigate increasingly complex environments. In particular, prefrontal cortical (PFC) regions undergo extensive remodeling as the brain is fine-tuned to orchestrate cognitive control over attention, reasoning, and emotions. Late adolescence also presents a uniquely vulnerable period as neurodevelopmental illnesses, such as schizophrenia, become evident and worsen into young adulthood. Challenges in early development, including prenatal exposure to infection, may set the stage for a cascade of maladaptive events that ultimately result in aberrant PFC connectivity and function before symptoms emerge. A growing body of research suggests that activation of the mother’s immune system during pregnancy may act as a disease primer, in combination with other environmental and genetic factors, contributing to an increased risk of neurodevelopmental disorders, including schizophrenia. Animal models provide an invaluable opportunity to examine the course of brain and behavioral changes in offspring exposed to maternal immune activation (MIA). Although the vast majority of MIA research has been carried out in rodents, here we highlight the translational utility of the nonhuman primate (NHP) as a model species more closely related to humans in PFC structure and function. In this review, we consider the protracted period of brain and behavioral maturation in the NHP, describe emerging findings from MIA NHP offspring in the context of rodent preclinical models, and lastly explore the translational relevance of the NHP MIA model to expand understanding of the etiology and developmental course of PFC pathology in schizophrenia.

      Keywords

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