Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice
Open accessAbstract
Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior (‘susceptible’) and those who escaped the deleterious effect to stress (‘resilient’). Myelin protein content in the nucleus accumbens was reduced in all mice exposed to stress, whereas decreased myelin thickness and internodal length were detected only in the medial prefrontal cortex (mPFC) of susceptible mice, with fewer mature oligodendrocytes and decreased heterochromatic histone marks. Focal demyelination in the mPFC was sufficient to decrease social preference, which was restored following new myelin formation. Together these data highlight the functional role of mPFC myelination as critical determinant of the avoidance response to traumatic social experiences. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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Chronic social defeat for up to two weeks is associated with reduction of myelination particularly in the mPFC, hippocampus and nucleus accumbens.
“Chronic social defeat for up to two weeks is associated with reduction of myelination particularly in the mPFC, hippocampus and nucleus accumbens [48,49]”
From Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies (2025) · cites this paper as [48]
The Results and discussion report a 10-day social-defeat protocol and reduced myelin basic protein in the nucleus accumbens of all defeated mice. In the mPFC, thinner myelin and shorter internodes were found only in susceptible mice; myelin basic protein levels did not significantly differ. The passages do not report a hippocampal reduction. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Bonnefil, V., Dietz, K., Amatruda, M., Wentling, M., Aubry, A. V., Dupree, J. L., Temple, G., Park, H.-J., Burghardt, N. S., Casaccia, P., & Liu, J.
- Affiliations
- The Graduate Center, CUNY (US)
- Icahn School of Medicine at Mount Sinai (US)
- Hunter College (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Liu, Jia
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2019-08-13
- Volume
- 8
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6692108
- OpenAlex
- W2967238306
- Cited by
- 123
- References
- 9
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 23 · 2023: 16 · 2022: 21 · 2021: 22 · 2020: 12 · 2019: 2
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (2R37NS042925-10, R01NS52738, CenterCore Grant 5P30 NS047463)
- National Cancer Institute (Cancer Center Grant P30 CAO16059)
- National Institute on Minority Health and Health Disparities (MD007599)
- City University of New York
- National Institute of Mental Health (R21MH114182)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- chronic social defeat stress, myelination, stress resilience, social avoidance, nucleus accumbens, medial prefrontal cortex, demyelination, oligodendrocytes, heterochromatin, histone modifications, mood disorders, social behavior
- MeSH terms
- Animals, Behavior, Animal, Demyelinating Diseases, Myelin Proteins, Myelin Sheath, Nucleus Accumbens, Social Behavior, Stress, Physiological, Mice
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