Related Experiment Video
Updated: Aug 14, 2026
Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice
Published on: August 13, 2020
Chronic social defeat reduces myelination in the mouse medial prefrontal cortex
Michael L Lehmann1, Thaddeus K Weigel1, Abdel G Elkahloun2
1Section on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, MD 20892 USA.
Abstract:
The medial prefrontal cortex (mPFC) plays a key role in top-down control of the brain's stress axis, and its structure and function are particularly vulnerable to stress effects, which can lead to depression in humans and depressive-like states in animals. We tested whether chronic social defeat produces structural alterations in the mPFC in mice. We first performed a microarray analysis of mPFC gene expression changes induced by defeat, and biological pathway analysis revealed a dominant pattern of down-regulation of myelin-associated genes. Indeed, 69% of the most significantly down-regulated genes were myelin-related. The down regulation was confirmed by in situ hybridization histochemistry for two strongly down-regulated genes, myelin oligodendrocyte glycoprotein (Mog) and ermin (Ermn), and by immunohistochemistry for myelin basic protein. To test for stress-induced changes in myelin integrity, aurophosphate (Black Gold) myelin staining was performed on mPFC sections. Quantitative stereologic analysis showed reduced myelinated fiber length and density. Behavioral analysis confirmed that the 14-day social defeat sessions resulted in induction of depressive-like states measured in social interaction and light/dark tests. The combined data suggest that chronic social defeat induces molecular changes that reduce myelination of the prefrontal cortex, which may be an underlying basis for stress-induced depressive states.
Insights
Chronic social defeat in mice reduces myelin in the medial prefrontal cortex (mPFC). This structural change in brain myelination is linked to depressive-like behaviors, offering insights into stress-related mood disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- The medial prefrontal cortex (mPFC) is crucial for regulating the stress axis and is vulnerable to stress.
- Stress-induced alterations in the mPFC can lead to depression in humans and depressive-like states in animals.
Purpose of the Study:
- To investigate whether chronic social defeat causes structural changes in the mPFC of mice.
- To explore the molecular mechanisms underlying stress-induced mPFC alterations.
Main Methods:
- Microarray analysis of mPFC gene expression following social defeat.
- In situ hybridization histochemistry and immunohistochemistry to confirm gene and protein expression changes.
- Aurophosphate (Black Gold) myelin staining and quantitative stereologic analysis to assess myelin integrity.
- Behavioral tests (social interaction, light/dark) to evaluate depressive-like states.
Main Results:
- Social defeat significantly down-regulated myelin-associated genes in the mPFC.
- Reduced expression of myelin oligodendrocyte glycoprotein (Mog) and ermin (Ermn) was confirmed.
- Myelin staining revealed decreased myelinated fiber length and density in the mPFC.
- Mice subjected to social defeat exhibited depressive-like behaviors.
Conclusions:
- Chronic social defeat induces molecular changes leading to reduced myelination in the medial prefrontal cortex.
- These structural alterations in mPFC myelination may represent a key mechanism underlying stress-induced depressive states.
