Effect of Prenatal Glucocorticoid Exposure on Circadian Rhythm Gene Expression in the Brains of Adult Rat Offspring
Bibliographic record
Abstract
Circadian clocks developed in organisms as a way of estimating the time of day. In mammals, the circadian clock is based on molecular oscillators that operate through transcriptional‐translational feedback loops. While normal circadian signaling relies on a ‘master clock’, in the suprachiasmatic nucleus (SCN), to synchronize peripheral oscillators to environmental light, glucocorticoid receptor (GR) signaling has the ability to reset the phase of peripheral clocks. GR is responsive to cortisol and is central to the regulation of genes involved in stress response, immune regulation and metabolism. Phase shifts allow peripheral clocks to become uncoupled from the master clock. The SCN does not express GR and this ensures it stays tied to the light‐dark cycle. It has been shown that maternal exposure to glucocorticoids (GCs) can lead to modification of hypothalamic‐pituitary‐adrenal (HPA) function and impact stress‐related behaviours via GR activation. While exploring the effects of prenatal GC exposure on rat offspring, our lab previously demonstrated altered circadian rhythm signaling in the adrenal glands using whole transcriptomic profiling. Pregnant WKY rats were given daily subcutaneous injections of 0.1 mg/kg/day DEX (Dexamethasone, a synthetic GC), or a saline vehicle throughout the third semester, and offspring sacrificed at 18 weeks of age for tissue collection. Brain regions were isolated through a micropunch technique and RNA extracted. Results from the current study show that prenatal GC exposure affects circadian rhythm gene expression in the molecular oscillators of the amygdala, hippocampus, prefrontal cortex, paraventricular nucleus as well as the main oscillator in the SCN. Transcripts of circadian rhythm genes in these tissues were measured through RT‐qPCR and demonstrated both sex and tissue specific alteration in expression of circadian genes including Bmal1, Clock, Npas2, as well as the Per and Cry genes. This widespread dysregulation of the circadian rhythm system points to a mechanism whereby the dysfunction seen previously in the adrenal gland arises from a programmed dysregulation of the entire circadian system beginning at the master clock in the SCN. Support or Funding Information Supported by grants from CIHR and NOSMFA Research Development Fund.
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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) | 0.002 | 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".