# Airway sensory nerve changes in a mouse model of maternal allergen exposure

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $47,998

## Abstract

Project Summary
Asthma is a pervasive public health problem, and affects over 10% of US citizens including 7 million children.
Children born to a mother with asthma have a significantly greater risk of developing asthma than children born
to fathers with asthma. This effect cannot be explained by genetic predisposition alone, suggesting there are
developmental, in utero exposures that predispose children to developing airway disease. Recently, adults with
asthma were found to have increased airway sensory innervation and worse airway obstruction, thus linking
airway sensory nerve remodeling to excessive bronchoconstriction in asthma. Furthermore, our preliminary
data indicate increased airway innervation develops in utero, suggesting that development of asthma in later
life is pre-programmed during fetal development.
To study the effects of maternal exposures on fetal development, we established a mouse model in which
offspring of mothers exposed to house dust mite allergen throughout pregnancy develop characteristic features
of human asthma, including airway hyperreactivity and increased sensory innervation. Airway hyperreactivity is
defined as greatly exaggerated bronchoconstriction (narrowing of the airways) in response to inhaled stimuli,
and it is mediated by a reflex that includes both sensory and parasympathetic nerves. The goal of this project
is to test the specific contribution of sensory nerve remodeling to excessive bronchoconstriction in adult mouse
offspring of these allergen exposed mothers, and to determine whether sensory nerve remodeling is reversible
in established disease.
In this proposal, I will distinguish between the contribution of sensory and parasympathetic nerves to airway
reactivity in adult offspring after maternal allergen challenge using pharmacological and surgical techniques, as
well as an innovative optogenetic approach that I developed. Since long-lasting airway nerve changes in
asthma are likely maintained by nerve growth factors, I propose to block brain derived neurotrophic factor
(BDNF), which is known to promote nerve growth and survival and which is also increased in patients with
asthma and in offspring from mothers exposed to allergen. I will test whether blocking BDNF reverses the
increased airway sensory innervation and airway hyperreactivity using our lab's novel imaging and
quantification techniques.
Taken together, achieving the goals of this project will: 1) define the neuronal mechanism for airway
hyperreactivity in offspring following maternal allergen exposure, 2) identify whether established neuronal
remodeling is reversible following BDNF antagonism, and 3) may lead to the development of new therapeutic
targets for childhood asthma.

## Key facts

- **NIH application ID:** 10459461
- **Project number:** 5F30HL145906-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Alexandra Bowman Pincus
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,998
- **Award type:** 5
- **Project period:** 2019-07-24 → 2023-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459461

## Citation

> US National Institutes of Health, RePORTER application 10459461, Airway sensory nerve changes in a mouse model of maternal allergen exposure (5F30HL145906-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459461. Licensed CC0.

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