Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis
Bibliographic record
Abstract
Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems related to mood disorders. PFOA exposure (5 mg/kg) for 10 consecutive days caused depression-like behaviors in male mice. We measured increased corticosterone in serum and in the hippocampus of PFOA-exposed mice, which were linked to enhanced CRF expression measured in the PVN. Elevated corticosterone was associated with reductions in glucocorticoid receptor (GR) protein expression within the hippocampus. CRFR1 antagonist injected into the PVN and intracerebroventricular (i.c.v.) GR antagonist both reduced depression-like behaviors, respectively. In addition, NMDA-dependent Schaeffer collateral-CA3 synaptic transmission in PFOA-exposed mice was disrupted. Synaptic deficits could be corrected by either CRFR1 or GR antagonists. In summary, we found exposure of male mice to PFOA enhances CRF expression, which then activates the HPA axis to disrupt GR expression in the hippocampus, leading to depression-like behaviors. This data is relevant for understanding the potential harmful health effects of PFOA.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. 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.
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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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 teacher head, 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".