Chronic Stress Induces Specific Cellular and Morphological Astroglial Changes Associated with Depressive-like Phenotypes
Year: 2019
Type: dissertation
Abstract: In major depressive disorder (MDD), one of the most consistent findings from post-mortem studies is decreased astroglia number and function in limbic brain regions including the prefrontal cortex (PFC). However, the contribution of astroglial pathology in synaptic dysfunction and depressive symptoms associated with MDD remains unclear. Here, using chronic restraint stress (CRS) in mice to model MDD, we demonstrate that CRS induced time-dependant decreases in astrocytic and synaptic protein expression in the PFC, which correlated with both anxiety- and anhedonia-like deficits. We also investigated CRS effects on astroglial cell morphology using Sholl analysis and found CRS decreased distal processes while increasing proximal processes. This structural rearrangement may parallel functional astrocytic and synaptic changes. Furthermore, we validated a custom-designed plasmid, allowing astroglial activity enhancement in vitro. This novel tool will allow us to test if PFC astroglial activation prevents CRS effects. This work substantiates astroglia as targets for antidepressant development.
Source: TSpace (University of Toronto)
Author: Dipashree Chatterjee
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3088195374