# Roles of Calprotectin in a mouse model of maternal immune activation

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $194,500

## Abstract

Abstract
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that currently lacks a fundamental
approach to treatment. To develop an effective therapeutic strategy, we need to understand the molecular
mechanism behind how ASD is established. It is known that infection during pregnancy increases the
probability of offspring developing ASD; therefore, we have been using a maternal immune activation (MIA)
model of ASD in mice. Using this model, we have found that the TLR3 ligand polyinosinic:polycytidylic acid
(Poly(I:C)) as well as virus can pass through the placenta and directly activate fetal border-associated
macrophages (BAMs) in the choroid plexus (CP) of the fetal brain. Furthermore, we have discovered that
TLR3-MIA increases the number of BAMs in the CP as well as increases their expression of S100a8 and
S100a9, which together forms a heterodimeric protein called calprotectin. Since increased calprotectin
expression is known to associate with chronic inflammatory conditions, we hypothesize that calprotectin
secreted from BAMs in the CP region may enhance inflammation in an autocrine manner and may also
function in a paracrine manner to disrupt the differentiation, migration, and proliferation of neural progenitor
cells (NPCs) in the periventricular area of the fetal brain. In this proposal, we will test our hypothesis by
measuring calprotectin protein levels in the cerebrospinal fluid in response to TLR3-MIA by ELISA (Aim 1) and
by investigating how calprotectin may influence NPC homeostasis in our TLR3-MIA model using single-nuclei
RNA-seq (Aim 2). If our hypothesis is correct, this work will be a first step toward developing a therapeutic
strategy for treating ASD by targeting calprotectin in the fetal brain.

## Key facts

- **NIH application ID:** 10749043
- **Project number:** 5R21HD107388-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** LAURENT COSCOY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,500
- **Award type:** 5
- **Project period:** 2022-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749043

## Citation

> US National Institutes of Health, RePORTER application 10749043, Roles of Calprotectin in a mouse model of maternal immune activation (5R21HD107388-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10749043. Licensed CC0.

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