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Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex
Sierra A Codeluppi1,2, Dipashree Chatterjee1,2, Thomas D Prevot1,3
1Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
The International Journal of Neuropsychopharmacology
|August 4, 2021
Summary
Chronic stress causes astrocyte atrophy in the prefrontal cortex, potentially linking to behavioral changes like anhedonia. This study reveals progressive glial cell changes with prolonged stress exposure.
Area of Science:
- Neuroscience
- Cell Biology
- Behavioral Science
Background:
- Neuromorphological changes in the prefrontal cortex are linked to stress-related disorders.
- The impact of stress on astrocyte morphology and its connection to behavioral deficits remain largely unexplored.
Purpose of the Study:
- To investigate the effects of chronic restraint stress (CRS) on astrocyte morphology in the prefrontal cortex.
- To determine the relationship between stress-induced astrocyte changes and behavioral deficits in mice.
Main Methods:
- Transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promoter were exposed to 7, 21, or 35 days of CRS.
- Behavioral tests (sucrose intake, PhenoTyper) assessed anhedonia- and anxiety-like behaviors.
- Sholl analysis evaluated prefrontal cortex astrocyte morphology (GFP+ and GFAP+ cells), with correlation analysis linking morphology to behavior.
Main Results:
- CRS induced anxiety-like behavior at all time points and anhedonia-like behavior by day 35.
- Significant atrophy of distal astrocyte processes was observed after 21 and 35 days of CRS.
- In males, astrocyte morphology changes significantly correlated with anhedonia-like behavior and overall behavioral deficits.
Conclusions:
- Chronic stress leads to progressive atrophy of cortical astroglial cells.
- This astrocyte atrophy may contribute to maladaptive neuroplasticity and behavioral changes seen in stress-related disorders.

