Cortical astrocytes control stress resilience.
Biorxiv : the Preprint Server for Biology
|February 6, 2026
Summary
Astrocytes in the prefrontal cortex (PFC) are crucial for stress resilience. Increased astrocytic calcium activity in the PFC promotes resilience, offering potential therapeutic targets for stress-related disorders.
Area of Science:
- Neuroscience
- Cell Biology
- Psychiatry
Background:
- Chronic stress is a risk factor for psychiatric disorders like PTSD and MDD.
- The prefrontal cortex (PFC) is key in mediating stress susceptibility.
- Astrocytes' role in stress resilience is largely unknown.
Purpose of the Study:
- Investigate the role of PFC astrocytes in stress resilience.
- Identify molecular mechanisms underlying stress resilience or susceptibility.
Main Methods:
- Utilized fiber photometry, chemogenetics, and RNA-sequencing in male mice.
- Assessed astrocytic calcium activity and transcriptional changes in the PFC.
- Compared PFC astrocyte data with human RNA-sequencing data from MDD patients.
Main Results:
- Stress-induced increases in astrocytic calcium activity are necessary and sufficient for resilience.
- PFC astrocytes show distinct transcriptional responses in resilient versus susceptible mice.
- Molecular changes in susceptible mice astrocytes overlap with gene expression in human MDD.
Conclusions:
- PFC astrocytes play a significant role in stress resilience.
- Targeting astrocytes may offer a therapeutic strategy for stress-induced disorders.
- Identified potential molecular pathways in PFC astrocytes linked to depressive behaviors.
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