Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation

Melissa D Bauman, Tyler A. Lesh, Douglas J. Rowland, Cynthia Schumann, Jason Smucny, David L. Kukis, Simon R Cherry, A Kimberley Usrey, Cameron S Carter

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Abstract

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [ 18 F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [ 18 F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [ 18 F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen’s d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence—a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge.

Original languageEnglish (US)
Article number135
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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