Long-Term Neuronal Effects Following Developmental Exposure to Low Levels of Persistent Organic Pollutants
Bibliographic record
Abstract
Introduction: Persistent organic pollutants (POPs) methylmercury (MeHg), polychlorinated biphenyls (PCBs), and organochlorines (OCs) are a significant problem in Arctic regions of Canada. The long-term impact of low-level developmental exposure to POPs on offspring is not clearly understood. The objective of the present thesis was to examine the long-term effects of low-level developmental exposure to POPs, alone or in mixtures, on selected markers of brain structure and function in the adult central nervous system (CNS). Method: Pregnant Sprague Dawley rats were exposed to one of four toxicant exposure conditions (MeHg, PCB, MeHg+PCB, or MeHg+PCB+OCs) at levels scaled to produce comparable maternal blood levels reported in epidemiological studies (or corn oil (control). Offspring were exposed to the toxicants from gestational day (GD) 1 to postnatal day (PND) 21 and thereafter with no further toxicant exposures aged to late adulthood (PND 450). The brain of adult offspring was fixed, frozen, and slide mounted for processing using immunohistochemistry and immunofluorescence techniques. A battery of markers of brain structure and function were assessed (glutamic acid decarboxylase (GAD)-67, glial cells (microglia, Bergmann glia), cleaved caspase-3, cresyl violet, doublecortin, double-stranded DNA (Hoechst), tyrosine hydroxylase, rat-endothelial cell antigen-1, lipofuscin). Eleven neuronal regions were included in the analysis. Digital image analysis was performed (ImageJ). Independent Samples T-tests compared toxicant-exposed animals with controls. Results: Most statistically significant observations were reported in neuronal regions localized in the brainstem. Across all four toxicant exposure groups (MeHg, PCB, MeHg+PCB, and MeHg+PCB+OC), a statistically significant increase in GAD67 was observed in the cerebellum, in comparison with controls. Likewise, a consistent decrease in lipofuscin autofluorescence was observed in the locus coeruleus in all toxicant-exposed offspring. Endothelial cell and capillary morphological marker RECA-1 was observed to be altered in a temporal manner with respect to neuronal development that corresponds to peak exposures to MeHg and PCBs. Toxicant mixtures (MeHg+PCB, MeHg+PCB+OC) resulted in comparatively fewer statistically significant changes in markers of brain structure and function than individual toxicant exposures (MeHg, PCBs). Conclusion: Altogether, the present study suggests that prenatal and early post-natal exposures to low levels of POPs may have lasting, selective, region-specific effects upon the CNS.
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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) | 0.001 | 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".