Astroglia Dysfunction in the Behavioural and Cellular Changes Associated with Chronic Stress
Bibliographic record
Abstract
Chronic stress alters the allostasis capabilities of individuals and is a major factor in the development of mood disorders such as major depressive disorder (MDD). In rodents, chronic stress models are used to understand the pathophysiology of MDD, as they induce comparable behavioural and cellular deficits. Since astroglia are involved in the maintenance of homeostasis, and neurotransmission, and support healthy neuronal functioning, it is not surprising that when affected by stress, astrocytes contribute to stress response and that their dysfunction is implicated in stress-related illnesses such as MDD. Rodents exposed to chronic stress exhibit a marked loss in glial fibrillary acidic protein (GFAP) astrocytes in the prefrontal cortex (PFC). As GFAP is a cytoskeletal protein expressed by astrocytes, it was postulated that chronic stress may also affect the morphology of astrocytes. Furthermore, previous studies attempting to determine if there was a causal relationship between astrocyte reductions and behaviour used pharmacological approaches to induce glial loss in key brain regions associated with stress. Specifically, non-specific gliotoxins used in the PFC to ablate glial cells have been shown to induce depressive-like deficits and impair cognitive flexibility. Although this study helped link the development of depressive-like behaviours specifically to glial cells, there is no data that specifically manipulates astrocytes as this has not been possible until recently with the development of new tools such as optogenetics and designer receptors exclusively activated by designer drugs (DREADD). Therefore, in this thesis, we investigated the link between the dysfunction of GFAP+ astrocytes and chronic stress-induced cellular and behavioural changes. Here, I determined that chronic stress induces PFC GFAP cell atrophy which correlates with anhedonia-like behaviour (Aim 1) and demonstrated that cell-specific ablation or activity enhancement of PFC GFAP+ cells induces anhedonia-like behaviour and reverses this deficit in chronic stress mice respectively (Aim 2). These studies contribute evidence linking anhedonia-like behaviour but not anxiety to PFC GFAP+ astroglia. The insights from this work further the understanding of the role of astroglia in stress-related illnesses and have the potential to improve treatment options for mood disorders by suggesting that targeting astroglia cells could be a novel avenue for drug discovery.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".