Early Environmental Regulation of Forebrain Glucocorticoid Receptor Gene Expression: Implications for Adrenocortical Responses to Stress; pp. 49–60
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- Meta-epidemiology (narrow)
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Other designConsensus signal: none
- Genre
- Candidate signal: ReviewConsensus signal: Review
- Teacher disagreement score
- 0.833
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.288 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
The adrenal glucocorticoids and catecholamines comprise a frontline of defense for mammalian species under conditions which threaten homeostasis (conditions commonly referred to as stress). Glucocorticoids represent the end product of the hypothalamic-pituitary-adrenal (HPA) axis and along with the catecholamines serve to mobilize the production and distribution of energy substrates during stress. The increased secretion of pituitary-adrenal hormones in response to stress is stimulated by the release of corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) from neurons in the nucleus paraventricularis. In this way, a neural signal associated with the stressor is transduced into a set of endocrine and sympathetic responses. The development of the HPA response to stressful stimuli is altered by early environmental events. Animals exposed to short periods of infantile stimulation or handling show decreased HPA responsivity to stress, whereas maternal separation, physical trauma and endotoxin administration enhance HPA responsivity to stress. In all cases, these effects persist throughout the life of the animal and are accompanied by increased hypothalamic levels of the mRNAs for CRH and often AVP. The inhibitory regulation of the synthesis for these ACTH releasing factors is achieved, in part, through a negative feedback loop whereby circulating glucocorticoids act at various neural sites to decrease CRH and AVP gene expression. Such inhibitory effects are initiated via an interaction between the adrenal steroid and an intracellular receptor (either the mineralocorticoid or glucocorticoid receptor). We have found that these early environmental manipulations regulate glucocorticoid receptor gene expression in the hippocampus and frontal cortex, regions that have been strongly implicated as sites for negative-feedback regulation of CRH and AVP synthesis. When the differences in glucocorticoid receptor density are transiently reversed, so too are those in HPA responses to stress. Taken together, our findings indicate that the early postnatal environment alters the differentiation of hippocampal neurons. This effect involves an altered rate of glucocorticoid receptor gene expression, resulting in changes in the sensitivity of the system to the inhibitory effects of glucocorticoids on the synthesis of CRH and AVP in hypothalamic neurons. Changes in CRH and AVP levels, in turn, determine the responsivity of the axis to subsequent stressors; increased releasing factor production is associated with increased HPA responses to stress. Thus, the early environment can contribute substantially to the development of stable individual differences in HPA responsivity to stressful stimuli. These data provide examples of early environmental programming of neural systems. One major objective of our research is to understand how such programming occurs within the brain.
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.
The record
- Venue
- Developmental Neuroscience
- Topic
- Neuroendocrine regulation and behavior
- Field
- Psychology
- Canadian institutions
- McGill UniversityDouglas Mental Health University Institute
- Funders
- National Institute of Mental HealthWellcome Trust
- Keywords
- EndocrinologyInternal medicineGlucocorticoid receptorForebrainVasopressinCorticotropin-releasing hormoneMineralocorticoid receptorGlucocorticoidHypothalamusBiologyAldosteroneCentral nervous systemMedicine
- Has abstract in OpenAlex
- yes