# Project 1: Maternal Immunity in MIA susceptibility

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $467,643

## Abstract

PROJECT SUMMARY – PROJECT 1
Maternal infection increases susceptibility of offspring to psychiatric and neurodevelopmental disorders,
including schizophrenia (SZ). Animal models of maternal immune activation (MIA) support this link, because
mid-gestational injection of poly(I:C) induces behavioral and neuropathological abnormalities in adult offspring
in domains similar to those affected in SZ. Thus, the poly(I:C) mouse model provides an opportunity to identify
the molecular and cellular underpinnings of susceptibility to MIA, which could lead to earlier diagnosis and
treatment of brain disease in humans. However, critical gaps in knowledge persist related to two of the most
important aspects of this risk factor for human disease: (i) most pregnancies are resilient to maternal infection
and (ii) susceptible pregnancies lead to multiple distinct disorders in offspring. We have recently discovered a
way to study both of these issues in the MIA mouse model. Results to date have revealed — for the first time
— an intrinsic factor, baseline immunoreactivity (BIR) of female mice before pregnancy, that, together with the
poly(I:C) dose used to induce MIA, predicts resilience as well susceptibility to neuropathology and aberrant
behaviors in offspring. These discoveries provide a unique opportunity to identify immune signatures before
and during pregnancy that underlie susceptibility and resilience to MIA, which can be used as biomarkers for
susceptible pregnancies. The central goal of this project is to identify the immune signaling pathways in
females before and during pregnancy that confer susceptibility or resilience to distinct subsets of MIA-induced
behavioral endophenotypes in offspring. We will address three specific aims: (i) identify immune biomarkers
and signaling pathways that underlie the range of BIR in female mice before pregnancy and that correlate with
susceptibility and resilience to MIA in offspring, (ii) identify how the progression of the maternal gestational
immune response in the mouse model dictates susceptibility or resilience to the effects of MIA in offspring, and
(iii) determine if BIR before pregnancy, and the maternal gestational immune response, correlate with
susceptibility or resilience to MIA in the non-human primate model. Project 1 directly addresses the central
hypothesis and all 3 aims of this Conte Center in a mechanistic manner by identifying immune signaling
pathways in females before and during pregnancy that confer susceptibility or resilience to distinct subsets of
MIA-induced neurodevelopmental and behavioral phenotypes in offspring. Results from this project are also
essential to the success of the other projects in the Center in revealing the immune signaling pathways that
drive susceptibility and resilience to sex-dependent changes in neural circuits (Projects 2, 4 and 5) and
neurodevelopmental and behavioral outcomes of offspring (Projects 2-5). Working closely with Project 2, we
will also test causality o...

## Key facts

- **NIH application ID:** 10378731
- **Project number:** 5P50MH106438-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JUDY A. VAN DE WATER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $467,643
- **Award type:** 5
- **Project period:** 2015-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378731

## Citation

> US National Institutes of Health, RePORTER application 10378731, Project 1: Maternal Immunity in MIA susceptibility (5P50MH106438-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378731. Licensed CC0.

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