# Role of adolescent stress in postpartum mood and cognition

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $74,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Mood disturbance and cognitive impairment during the postpartum period are common and serious problems in
women’s mental health. Early life stress, such as psychosocial stress during adolescence, increases the risk for
postpartum emotional and cognitive problems in humans, including the development of postpartum mood
disorders. Nonetheless, the biological mechanisms linking adolescent stress to postpartum emotional and
cognitive abnormalities are not well understood. Our long-term goal is to examine how pre-partum life stress
affects hormonal systems, neural function, and behaviors in the developmental trajectory from adolescence to
the postpartum period and dissect the mechanisms from molecules to circuits and behavior. Human imaging
studies have linked functional changes in the projections from the anterior insula (AI) to dorsal anterior cingulate
cortex [dACC, homologous to the prelimbic cortex (PrL) in rodents] to postpartum behavioral changes. Elevated
levels of glucocorticoids by disturbance of negative feedback of the hypothalamic-pituitary-adrenal axis during
the postpartum period can alter neural function. To gain more biological insight into these points, we have built a
novel platform to study the biological mechanisms underlying the effects of adolescent stress on postpartum
emotional and cognitive behaviors in first-time mothers, based on the adolescent social isolation paradigm we
have already published. Hence, our current objective is to test the hypothesis that adolescent stress, in
conjunction with the stressful events of pregnancy/delivery, leads to deficits in postpartum behaviors related to
mood and social cognition via glucocorticoid-mediated functional alterations of AI-PrL glutamatergic projections.
To address this hypothesis, we will pursue the following specific aims: In Aim 1, we will examine the role of
AI-PrL projections in adolescent stress-induced PrL dysfunction and behavioral deficits in adult postpartum
mice using a combination of state-of-the-art techniques, including in vivo calcium imaging in conjunction with
projection-specific neuronal manipulation in freely moving mice. In Aim 2, we will determine the role of
glucocorticoid receptor (GR) in adolescent stress-induced PrL dysfunction and behavioral deficits in adult
postpartum mice. In Aim 3, we will combine retrograde tracing and cell type-specific manipulation using the
green fluorescent protein (GFP)-dependent Cre recombinase system to examine the causal role of
GR-mediated AI-PrL glutamatergic projections in the PrL dysfunction and behavioral deficits in adult postpartum
mice pre-exposed to adolescent isolation rearing. Our findings may provide biological insights into postpartum
mood disturbance and cognitive impairment, which are highly prevalent and have deleterious effects not only on
the mother, but also on the children and the rest of the family. These findings will have a broad impact on the
well-being of women and children ...

## Key facts

- **NIH application ID:** 10165040
- **Project number:** 3R01MH116869-02S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Minae Niwa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,250
- **Award type:** 3
- **Project period:** 2020-07-09 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165040

## Citation

> US National Institutes of Health, RePORTER application 10165040, Role of adolescent stress in postpartum mood and cognition (3R01MH116869-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165040. Licensed CC0.

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