# Alterations in primate brain development following prenatal immune challenge

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $800,943

## Abstract

ABSTRACT
Prenatal exposure to viral or bacterial infections during pregnancy is associated with an increased risk of
offspring neurodevelopmental disorders, including autism and schizophrenia. Gestational biomarkers indicate
that the maternal immune response is the critical link between maternal infection and altered offspring
neurodevelopment. However, our ability to mitigate the deleterious impact of maternal infection on offspring
brain development is severely restricted by our limited mechanistic understanding of the underlying
neurobiological changes. Although preclinical rodent models have provided foundational evidence of
alterations in brain and behavioral development resulting from MIA exposure that mirror some changes in
human disorders, translational limitations provide a need to extend this program of research into a species
more closely related to humans. Nonhuman primates (NHPs) provide the closest model to human
development, sharing similarities in placental structure and pregnancy physiology, maternal-fetal interface,
gestational timeline, fetal and postnatal brain development, and complex social behavior and cognition. Our
laboratory has developed the first viral-mimic based NHP MIA model and demonstrated that MIA-exposed
NHPs exhibit alterations in brain and behavioral development implicating selective vulnerability to
socioemotional amygdala-prefrontal circuitry. Here we propose to leverage the entire biorepository of brain
tissue from previous NHP MIA models to determine, at the single cell level, the transcriptomic, cellular, and
connectomic alterations triggered by prenatal immune challenge. We have developed a novel pipeline for a
genes-to-circuitry approach that maximizes the yield of information from this precious tissue resource. Here,
we will target key brain regions in the amygdala-prefrontal network mediating socioemotional behaviors
implicated in human neurodevelopmental and mental health disorders at two critical age time points for the
pathophysiology of mental illness: juvenile (18 month) and adolescent (4 year). We will generate single-nuclei
transcriptomic profiles and quantify differentially expressed genes (DEGs) in specific cell types (Aim 1),
spatially map and quantify high-priority transcripts in specific cell types and within-cell transcriptomic
colocalization (Aim 2), and map spatial distribution of synaptic composition, receptors, and direct inputs onto
specific cell types (Aim 3). These data, in combination with the extensive, longitudinal characterization of
offspring brain and behavioral development, build a comprehensive picture of MIA-induced changes in NHP
brain circuitry, toward the ultimate goal of identifying pathways of vulnerability and critical periods for novel,
targeted interventions and biotherapeutics to reduce the number of children adversely affected by prenatal
exposure to maternal infection.

## Key facts

- **NIH application ID:** 10930951
- **Project number:** 5R01MH135390-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Melissa Dawn Bauman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $800,943
- **Award type:** 5
- **Project period:** 2023-09-18 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930951

## Citation

> US National Institutes of Health, RePORTER application 10930951, Alterations in primate brain development following prenatal immune challenge (5R01MH135390-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10930951. Licensed CC0.

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