# Prenatal neuroinflammation: maternal microbiome contributions and behavioral consequences

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $544,156

## Abstract

Summary: Prenatal stress is pervasive and negatively impacts both the mother and the developing fetus;
offspring bear an increased risk of aberrant neurodevelopment and psychiatric disorders. Indeed, there is a
critical window in utero where neurodevelopment is vulnerable to stress-induced alterations in the intrauterine
environment, including inflammation; how alterations in the maternal milieu are transmitted to the developing
brain, contributing to behavioral alterations, requires scrutinizing. We have established a mouse model of
prenatal stress, which in addition to altering maternal and offspring microbiota, induces inflammation in utero,
including increases in the chemokine C-C motif chemokine ligand 2 (CCL2), resulting in reduced social
behaviors and longstanding neuroinflammation. Furthermore, we have exciting supporting and preliminary data
suggesting that normal neurodevelopment is disrupted by prenatal stress in a microbe- and CCL2-dependent
manner. As a chemokine, CCL2 has a key role in both attracting myeloid cells and enhancing their
inflammatory profile. Within the brain, the myeloid compartment includes microglia, the resident macrophages
of the central nervous system; border-associated macrophages (BAMs), which are found in the perivascular
space, choroid plexus, and meninges; and circulating monocytes. However, the effects of prenatal stress and
CCL2 on the composition of and cytokine production by these subpopulations has yet to be elucidated, and is
critical as cytokine signaling is important for homeostatic functions during neurodevelopment, including
regulating neuro- and gliogenesis. Therefore, the goal of this R01 is to investigate the relationship between
prenatal stress, brain macrophages and monocytes, and social behavior. Our model of prenatal stress will be
used to test the highly novel, and integrative hypothesis that, during prenatal stress, there are alterations in the
composition of brain macrophages and monocytes in the fetal brain, increasing cytokine production, influencing
neurodevelopment. Next, we will determine whether cell-specific elimination of CCL2 production is able to
prevent neuroinflammation and subsequent alterations in social behavior. Finally, in an exploratory aim, we will
test whether alterations in the maternal microbiome are necessary and sufficient to induce the persistent
neuroinflammation and concomitant reduction in social behavior in adult offspring. Our overarching
hypothesis is that prenatal stress leads to fetal neuroinflammation that results in long term behavioral
abnormalities by altering the composition of macrophages and monocytes in the developing brain and
increasing their inflammatory profile, which is driven by disruption of maternal microbes and CCL2.
This hypothesis will be tested by pursuing these aims: 1) Determining whether prenatal stress alters the
composition of fetal brain macrophages and monocytes 2) Elucidating whether CCL2 drives inflammation in
fetal macrophages...

## Key facts

- **NIH application ID:** 10799709
- **Project number:** 5R01MH129589-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Tamar Gur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $544,156
- **Award type:** 5
- **Project period:** 2022-05-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799709

## Citation

> US National Institutes of Health, RePORTER application 10799709, Prenatal neuroinflammation: maternal microbiome contributions and behavioral consequences (5R01MH129589-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10799709. Licensed CC0.

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