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Profiling changes in cortical astroglial cells following chronic stress
Stephanie Simard1, Gianfilippo Coppola2, Christopher A Rudyk1
1Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
Summary
Chronic variable stress (CVS) alters genes in cortical astroglia, impacting neuroplasticity and depressive behaviors. Targeting astroglial plasticity, particularly perineuronal nets, may offer new depression treatments.
Area of Science:
- Neuroscience
- Cell Biology
- Psychiatry
Background:
- Cortical astroglia are implicated in depressive behaviors.
- Their specific roles in neuroplasticity and depression remain unclear.
- Understanding astroglial mechanisms is crucial for developing novel depression therapies.
Purpose of the Study:
- To investigate changes in astroglial gene expression during depressive-like behaviors.
- To identify specific astroglial pathways involved in stress-induced depression.
- To explore the role of astroglia-associated extracellular matrix in depression.
Main Methods:
- Utilized astroglial-specific bacTRAP mice subjected to chronic variable stress (CVS).
- Employed translating ribosome affinity purification (TRAP) coupled with RNA sequencing (RNAseq) to profile astroglial translatomes.
- Validated findings by assessing perineuronal nets (PNNs) and their degradation in the prefrontal cortex.
Main Results:
- CVS induced depressive-like behaviors and increased corticosterone levels.
- Astroglial gene expression showed decreased plasticity-associated genes and increased extracellular matrix genes, including those for PNNs.
- Increased PNNs in the prefrontal cortex were observed following CVS.
- Degrading PNNs reversed CVS-induced behavioral changes in the forced swim test.
Conclusions:
- Cortical astroglial plasticity is reduced following chronic stress, contributing to depressive behaviors.
- Astroglia-mediated changes in extracellular matrix, specifically PNNs, play a significant role in depression.
- These findings support the neuroplasticity hypothesis of depression and suggest astroglia as potential therapeutic targets.
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