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Updated: Jun 5, 2026
Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Effects of neonatal stress and morphine on murine hippocampal gene expression
Sandra E Juul1, Richard P Beyer, Theo K Bammler
1Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. sjuul@uw.edu
Insights
Neonatal stress impacts hippocampal gene expression, affecting pathways like fear response and brain development. Morphine alters these stress-induced changes, with combined stress and morphine showing unique effects on mitochondrial and developmental gene sets.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Critically ill preterm infants face significant stressors during hospitalization.
- Morphine is frequently used to manage pain and stress in these infants.
- Understanding the molecular impact of stress and morphine on the developing brain is crucial.
Purpose of the Study:
- To investigate the dose-dependent effects of neonatal stress on hippocampal gene expression.
- To determine how morphine treatment modifies stress-induced changes in hippocampal gene expression.
- To identify potential interactions between stress and morphine on neurodevelopmental pathways.
Main Methods:
- Male C57BL/6 mice were subjected to control, mild stress, severe stress, or stress with morphine treatment between postnatal days 5-9.
- Hippocampal RNA was extracted and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays.
- Gene expression changes were analyzed using single gene and gene set analyses, with qPCR validation.
Main Results:
- Neonatal stress alone altered gene sets associated with fear response, oxygen transport, and NMDA receptor synthesis.
- Morphine treatment down-regulated gene sets involved in immune function.
- Combined stress and morphine treatment uniquely affected mitochondrial electron transport and down-regulated brain development and growth gene sets.
Conclusions:
- Neonatal stress significantly influences hippocampal gene expression patterns.
- Morphine partially alters stress-related gene expression changes and affects independent gene sets.
- The combination of stress and morphine induces interaction effects on gene expression not observed with either stimulus alone, potentially impacting neurodevelopment.
Abstract:
Critically ill preterm infants experience multiple stressors while hospitalized. Morphine is commonly prescribed to ameliorate their pain and stress. We hypothesized that neonatal stress will have a dose-dependent effect on hippocampal gene expression, and these effects will be altered by morphine treatment. Male C57BL/6 mice were exposed to five treatment conditions between postnatal d 5 and 9: 1) control, 2) mild stress + saline, 3) mild stress + morphine, 4) severe stress + saline, and 5) severe stress + morphine. Hippocampal RNA was extracted and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays. Single gene analysis and gene set analysis were used to compare groups with validation by qPCR. Stress resulted in enrichment of gene sets related to fear response, oxygen carrying capacity, and NMDA receptor synthesis. Morphine down-regulated gene sets related to immune function. Stress + morphine resulted in enrichment of mitochondrial electron transport gene sets and down-regulation of gene sets related to brain development and growth. We conclude that neonatal stress alone influences hippocampal gene expression, and morphine alters a subset of stress-related changes in gene expression and influences other gene sets. Stress + morphine show interaction effects not present with either stimulus alone. These changes may alter neurodevelopment.
