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Prefrontal cortex astroglia modulate anhedonia-like behavior
S A Codeluppi1,2, M Xu3, Y Bansal1
1Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
Molecular Psychiatry
|September 11, 2023
Summary
Reduced glial fibrillary acidic protein (GFAP) expressing astroglia in the prefrontal cortex (PFC) are linked to depression. This study shows PFC astroglia depletion causes anhedonia, while enhancing their activity reverses stress-induced anhedonia.
Area of Science:
- Neuroscience
- Cell Biology
- Psychiatry
Background:
- Reductions in glial fibrillary acidic protein (GFAP)-expressing astroglia are observed in the prefrontal cortex (PFC) of individuals with depression.
- Similar astroglial changes are noted in rodent models of chronic stress, suggesting a role in depressive disorders.
Purpose of the Study:
- To investigate the functional impact of prefrontal cortex (PFC) astroglia, specifically those expressing GFAP, on depressive-like behaviors in rodents.
- To determine if modulating PFC GFAP+ cell activity can influence anhedonia and anxiety-like behaviors.
Main Methods:
- Experimental depletion of PFC GFAP+ cells using viral-mediated expression of the diphtheria toxin receptor followed by diphtheria toxin administration.
- Enhancement of PFC GFAP+ cell activity using designer receptor exclusively activated by designer drugs (DREADDs) in a chronic stress model.
Main Results:
- PFC GFAP+ cell depletion induced significant anhedonia-like behavior, which persisted for up to 8 days, without affecting anxiety-like behaviors.
- Activation of PFC GFAP+ cells using DREADDs successfully reversed anhedonia-like deficits caused by chronic restraint stress, but did not alter anxiety-like behaviors.
Conclusions:
- Cortical astroglia play a critical role in the pathophysiology of anhedonia, a core symptom of depression.
- Targeting astroglia represents a potential therapeutic strategy for treating depression, particularly symptoms related to anhedonia.
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