A276 CANNABINOID RECEPTOR 1 IS LOCALIZED IN ENTERIC NEURONS AND EPITHELIUM IN FETAL AND EARLY POSTNATAL MOUSE INTESTINE
Bibliographic record
Abstract
Abstract Background The endocannabinoid system (ECS) is necessary for gastrointestinal (GI) homeostasis and serves as a target for exogenous medicinal and recreational cannabinoid compounds. While components of the ECS, including receptors, ligands, and biosynthetic/degradative enzymes, have been increasingly characterized in the adult GI tract of both humans and animal models, similar advances in understanding the role of the ECS in GI developmental programming have not yet been made. Purpose We tested the hypothesis that the ECS plays a role in the developmental programming of the GI tract. Method The developmental timeline of ECS component expression was investigated in the GI tract from fetal and early postnatal mice. Samples from timed-pregnant outbred mice were collected from embryonic days 14 (E14), E16, E18 and postnatal days 1 (P1), P7 and P28, representing a timeline of early colonization of the GI tract by enteric neurons (E14) to 1 week after weaning (P28). Localization of cannabinoid receptor 1 (CB1) expression was examined in fetal and postnatal small intestine by immunohistochemistry. Fetal intestine was processed for RNA extraction and relative expression of ECS components determined by RT-qPCR. Result(s) CB1 expression at E14 was observed in the outer wall of the gut and in the developing mucosa. By E18, expression of CB1 became more localized to the enteric plexuses and to mucosal epithelial cells. In postnatal ileum, at least >50% of myenteric ganglia were found to express CB1 from P1 to P28. CB1 expression continued to be present in the mucosal epithelium of ileum from P1 to P28, with a subset of CB1 expression in enterochromaffin cells, as identified by 5-HT immunolabeling. Significant decreases in expression of mRNA encoding CB1 (p<0.0001) and the ECS biosynthetic enzymes NAPE-PLD (p<0.05) and DAGLa (p<0.05) were found between E14 and E18. Conclusion(s) Components of the ECS are present in the fetal and early postnatal GI tract. Further research is needed to better characterize the roles and mechanisms of action of the ECS in GI development. The potential impact of exogenous cannabis exposure in early life, either by in utero exposure or via the use of medicinal cannabinoids in childhood, highlights the importance of identifying the contributions of the ECS to normal development. Disclosure of Interest None Declared
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".