Transgenerational Inheritance of Cognitive Deficits Induced by Ancestral Arsenic Exposure in Zebrafish (<i>Danio rerio</i>) via Maternal and Paternal Lineages
Bibliographic record
Abstract
Exposure to arsenic is known to impair learning and memory functions in animal models and humans. However, the transgenerational inheritance of these cognitive deficits and the underlying epigenetic mechanisms remain poorly understood. The present study investigated the inter- and transgenerational effects of ancestral arsenic exposure on the cognitive performance (latent learning) of zebrafish via maternal and paternal lineages and the underlying biochemical and molecular alterations in the brain, including the DNA methylation patterns of cognition-related genes. Adult male zebrafish exposed to dietary arsenic [30, 60, or 100 μg/g as arsenite for 90 days; F 0 generation] were crossed with unexposed (control) females and vice versa to generate F 1 progeny of maternal and paternal arsenic exposure, respectively. Subsequently, F 1 males and females of the same treatments were crossed to generate the F 2 progeny of the respective maternal and paternal lineages of ancestral arsenic exposure. It was found that ancestral arsenic exposure induced cognitive dysfunction in F 1 and F 2 generations of both maternal and paternal lineages. However, the effects occurred at relatively lower levels of ancestral arsenic exposure (30 and 60 μg/g) in the former treatment relative to those (100 μg/g) in the latter. Inter (F 1 ) and transgenerational (F 2 ) cognitive effects of arsenic were associated with concomitant elevated oxidative stress and dopaminergic dysregulation, including repressed expression of cognition-related genes such as genes involved in dopamine signaling and metabolism ( Drd1 and MAO ) and the brain-derived neurotrophic factor ( BDNF ). Furthermore, DNA methylation analyses revealed that the downregulation of these genes across three generations (F 0 to F 2 ) resulted from the hypermethylation in their promotor regions ( Drd1, MAO, BDNF ). Collectively, these observations provide novel insights into the epigenetic mechanisms of the transgenerational inheritance of arsenic neurotoxicity.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".