A Further Analysis and Commentary on: Profiling Changes in Cortical Astroglial Cells Following Chronic Stress

Abstract

The neuroplasticity hypothesis of depression proposes that major depressive disorders are related to decreased hippocampal and cortical neural plasticity, which is reversed by antidepressant treatment. Astroglial cells have emerged as key mediators of neural plasticity and are involved in the cause and treatment of depression and anxiety-like behaviors. One of the ways that astroglia modulate neuroplasticity is through the formation and maintenance of perineuronal nets (PNNs). Perineuronal nets are important extracellular matrix components that respond to stress and are implicated in anxiety-like behaviors. Normally, astroglial cells continuously turnover PNNs by degrading and donating PNN proteins; however, chronic stress slows PNN protein degradation and increases cortical PNN expression overall. In this report, we used weighted gene co-expression network analysis and eigengene analysis to further delineate the pathways and key regulators involved in the astroglial-PNN relationship following chronic stress. Our analyses indicate that chronic variable stress induces the expression of PNNs through inhibition of trophic pathways and key transcription factors in astroglial cells. These data further support the integral role of astroglial cells in the neuroplasticity hypothesis of depression through their modulation of anxiety-like behaviors and PNNs.

Depression and Quality of Life in Patients with Gliomas: A Narrative Review

“…It can act at different stages of the carcinogenesis of glioma and neuroblastoma, affecting signal transduction in normal cells, promoting the proliferation and survival of cancer cells, and releasing cytokines and soluble mediators that favor tumor growth [ 50 ]. The involvement of astrocytes in depression has been reported, but valuable studies on the relationship between the genetic component of depression and glioma development and progression are still lacking [ 59 , 60 , 61 ]. Coppola et al [ 59 ] used bioinformatics analysis to further delineate the key mediators involved in the astrocyte–peripheral neural nets–depression relationship and identified important transcription factors in astrocytes [ 59 , 60 ].…”

“…The involvement of astrocytes in depression has been reported, but valuable studies on the relationship between the genetic component of depression and glioma development and progression are still lacking [ 59 , 60 , 61 ]. Coppola et al [ 59 ] used bioinformatics analysis to further delineate the key mediators involved in the astrocyte–peripheral neural nets–depression relationship and identified important transcription factors in astrocytes [ 59 , 60 ]. Fibroblast growth factors (FGFs) and their receptors have been shown to be involved in the pathogenesis of neurological diseases.…”

Insights Into Translatomics in the Nervous System

“…Analysis of top DEGs indicated that CVS impaired perineuronal net (PNN) degradation, resulting in neuroplastic dysfunction ( Simard et al, 2018 ). Subsequently, based on the same database, Coppola et al used bioinformatics analysis to further delineate key mediators involved in the astroglial-PNN-depression relationship and found important transcription factors in astroglial cells ( Coppola et al, 2019 ). In addition to PNN, the serotonin system plays a critical role in the pathogenesis of stress, but therapies that target the stress and depression associated genes such as Tph2 and Slc6a4 (SERT) to modulate serotonin reuptake and degradation have no obvious effect in clinical trials ( Lalovic and Turecki, 2002 ; Bellivier et al, 2004 ; Oquendo et al, 2014 ).…”

The Role of Prefrontal Cortex Astroglial Glucocorticoid Receptors in Mediating the Effects of Chronic Variable Stress on Emotive Behaviour

“…In this way estrogens can interact with astroglial ERs to modulate EI balance via glutamate and calcium. Work from our lab has shown that estrogen modulates the expression of GFAP and FGF2 within the cortex and that estrogen directly modulates the transcription of GFAP (Simard et al, 2018;Coppola et al, 2019). Together this data suggests a relationship between ESR1, astrocytes and depression that merits further investigation.…”

“…Further analysis of this translatomic data using weighted gene co-expression network analysis (WGCNA) revealed five distinct modules associated with CVS-induced changes (Coppola et al, 2019). The differentially expressed genes (DEGs) within these modules were associated with ECM proteoglycans and astroglial activation, lysosome and protein transport, MAP kinases and RhoGTPases, signaling growth factors, regulation of transcription, and enrichment of metabolic pathways.…”