# An Examination of Oxytocin as a Neuroprotective Factor for the Development of Perineuronal Nets Using an Animal Model to Simulate Birth Interventions

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $199,922

## Abstract

Abstract
The hormone oxytocin has several adaptive functions at birth. The experiments
proposed here stem from both exciting new research describing oxytocin's
neuroprotective role for the fetal brain at birth and recent studies indicating that normal
perineuronal net (PNN) architecture is essential for proper cognitive and emotional
processing. PNNs are extracellular matrix complexes that enwrap fast-spiking,
parvalbumin-positive interneurons (PVIs) and provide synaptic and network stability.
While PNNs protect neurons against oxidative damage, PNNs themselves are sensitive
to oxidative stress during development and their degradation is associated with altered
interneuron circuitry, as well as enhanced microglial activation. Importantly, aberrant
PNN structure and interneuron circuitry, as well as exaggerated microglial activation, are
linked with neurodevelopmental disorders, psychiatric disorders and cognitive
dysfunction. Interestingly, oxytocin signaling at birth buffers the fetal brain against
oxidative stress, suggesting that this hormone may protect developing PNNs/PVIs. The
regular use of synthetic oxytocin (sOT; Pitocin) to induce or augment labor, as well as
the common occurrence of pre-labor cesarean sections, alter fetal exposure to oxytocin
during delivery. However, how these OT-related birth manipulations affect the
development of neural architecture of offspring remains largely unexplored in both
animal models and humans. Because of OT's neuroprotective role, we hypothesize that
OT-related manipulations at birth alter oxidative stress exposure and PNN formation. In
Aim 1, we will examine the dose-dependent effects of sOT administration at birth on
oxidative stress and microglial activation, postnatal development of PVIs and PNNs, and
social behavior within offspring. In Aim 2, we will determine a) if a pre-labor cesarean
delivery increases fetal oxidative stress exposure and microglial activation, disrupts
postnatal development of PVIs and PNNs, and alters social behavior within offspring and
b) if perinatal administration of OT shortly after a pre-labor C-section can rescue the
predicted neural and social behavioral changes. The purpose of this proposal is to
determine whether birth-related interventions that modulate oxytocin signaling during
delivery alter a specific neural mechanism (PNN/PVI formation). Data from this study will
inform our current understanding of the normal development of neural architecture and
aid in the evaluation of treatments used to manipulate the birth process.

## Key facts

- **NIH application ID:** 10227906
- **Project number:** 5R21HD098603-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Marcy A Kingsbury
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,922
- **Award type:** 5
- **Project period:** 2020-08-03 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227906

## Citation

> US National Institutes of Health, RePORTER application 10227906, An Examination of Oxytocin as a Neuroprotective Factor for the Development of Perineuronal Nets Using an Animal Model to Simulate Birth Interventions (5R21HD098603-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10227906. Licensed CC0.

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