# Implications of Maternal Baseline Immunoreactivity in the Susceptibility and Resilience to Behavioral and Circuit-wide Consequences of Maternal Immune Activation

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $39,667

## Abstract

Project Summary/Abstract
Maternal infection and fever increase susceptibility of offspring to several brain disorders including autism
(ASD), schizophrenia (SZ), and major depression (MDD). Animal models of maternal immune activation (MIA)
support this link, as mid-gestational injection of the viral mimic, poly(I:C), induces a wide range of disease-
related behavioral and neuropathological abnormalities in adult offspring. Yet, current approaches using this
model ignore two of the most important aspects of human psychiatric illness: (i) most pregnancies are resilient
to maternal viral infection and (ii) susceptible pregnancies can lead to multiple neurodevelopmental and
psychiatric disorders in offspring. Our laboratory has recently discovered a way to study both of these issues in
the MIA mouse model. We have recently found that virgin female C57/B6 mice exhibit a wide range of baseline
immunoreactivity (BIR) that dictates susceptibility or resilience of subsequent pregnancies to MIA-induced,
disease-related outcomes in offspring. Surprisingly, intermediate (but not low and high) poly(I:C) doses are
selectively effective at increasing repetitive behaviors in adult male offspring and offspring exposed to the
same intermediate dose during gestation exhibit distinct subsets of abnormal behaviors that are reproducibly
predicted by the BIR of the dam. These results have revealed, for the first time, a factor (BIR) that confers
resilience as well susceptibility to specific combinations of endophenotypes in MIA offspring. The central goals
of my project are to identify the striatal connectivity changes in offspring and the role of interleukin-6 (IL-6)
signaling in the dam that confer resilience or susceptibility to specific combinations of MIA-induced behavioral
outcomes. In Aim 1, I will determine if the magnitude of MIA predicts resilience and susceptibility of offspring to
behavioral deficits, and whether susceptible individuals show distinct, BIR-driven behavioral signatures. In Aim
2, I will determine whether MIA results in distinct connectivity changes in afferent neurons, dopaminergic
circuits, synapse density and balance of excitatory and inhibitory synapses in striatum using array tomography
and retrograde viral tracing. Finally, in Aim 3, I will employ a combination of experiments utilizing IL-6
supplementation and inhibition to reveal whether IL-6 alone is necessary and sufficient to dictate susceptibility
and resilience to alterations in striatal dependent behaviors and circuitry. Most important, I will determine if
manipulation of IL-6 levels can convert susceptible pregnancies into resilient ones. If successful, my project
may identify biomarkers to predict pregnancies most at risk and approaches to prevent offspring from
developing psychiatric disorders.

## Key facts

- **NIH application ID:** 10450068
- **Project number:** 5F31MH123106-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Kathryn Elizabeth Prendergast
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,667
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450068

## Citation

> US National Institutes of Health, RePORTER application 10450068, Implications of Maternal Baseline Immunoreactivity in the Susceptibility and Resilience to Behavioral and Circuit-wide Consequences of Maternal Immune Activation (5F31MH123106-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450068. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*